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Genetics and Molecular Biology

Print version ISSN 1415-4757On-line version ISSN 1678-4685

Genet. Mol. Biol. vol.31 no.2 São Paulo  2008

http://dx.doi.org/10.1590/S1415-47572008000300002 

REVIEW ARTICLE

 

"Adaptive response" - some underlying mechanisms and open questions

 

 

Evgeniya G. DimovaI; Peter E. BryantII; Stephka G. ChankovaI

IDepartment of Bioindication and Environmental Risk, Central Laboratory of General Ecology, Bulgarian Academy of Sciences, Sofia, Bulgaria
IIBute Medical School, University of St. Andrews, St. Andrews, Scotland, UK

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ABSTRACT

Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e.g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses - DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.

Key words: adaptive response, oxidative stress, DNA repair up-regulation, DNA-binding proteins, antioxidant defense system.


 

 

The adaptive response

Organisms are affected by various different physical and chemical genotoxic agents, some of them natural (e.g. solar ultraviolet light, ionizing radiation) and others released in the environment as a result of human activity (anthropogenic environmental pollutants). Many defense mechanisms have evolved to minimize genotoxic damage. One of these is induced radioresistance or adaptive response (AR). The term "adaptive response" usually means that a relatively small "conditioning" radiation dose induces increased radioresistance when the cells are irradiated with higher doses several hours later (Hillova and Drasil, 1967). Thus, radioadaptive response induction expresses the ability of low dose radiation to induce cellular changes that alter the level of subsequent radiation-induced or spontaneous damage. The AR could be considered a nonspecific phenomenon - the exposure to minimal stress inducing a very low level of damage can trigger an AR resulting in increased resistance to higher levels of the same or of other types of stress (Joiner et al., 1996; Wolff, 1998; Joiner et al., 1999; Patra et al., 2003; Asad et al., 2004; Girigoswami and Ghosh, 2005; Yan et al., 2006).

The AR has been observed in many different organisms: bacteria, yeast, the algae Oedogonium cardiacam, Chlamydomonas reinhardtii, Closterium monoliferum and Chlorella pyrenoidosa, in higher plants, insect cells, mammalian cells, human cells in vitro, and in animal models in vivo during a protracted (low dose-rate) exposure prior to an acute dose treatment (Horsley and Laszlo, 1971, 1973; Bryant, 1974, 1975, 1976, 1979; Howard and Cowie, 1976, 1978; Olivieri et al., 1984; Santier et al., 1985; Wolff et al., 1988; Boreham and Mitchel, 1991; Rieger et al., 1993; Mahmood et al., 1996; Salone et al., 1996; Panda et al., 1997; Asad et al., 1997, 1998; Wolff, 1998; Nikolova et al., 1999; Wang and Cai, 2000; Sawant et al., 2001; Tiku and Kale, 2001, 2004; Venkat et al., 2001; Assis et al., 2002; Chankova and Bryant, 2002; Gajendiran and Jeevanram, 2002; Rubinelli et al., 2002; Schlade-Bartusiak et al., 2002; Sedgwick and Lindahl, 2002; Jovtchev and Stergios, 2003; Patra et al., 2003; Savina et al., 2003; Ulsh et al., 2004; Zhou et al., 2004; Atanasova et al., 2005; Chankova et al., 2005, 2007; Coleman et al., 2005; Friesner et al., 2005; Lanza et al., 2005; Rohankhedkar et al., 2006; Seo et al., 2006).

Different endpoints have been used to demonstrate an AR: cell survival, gene mutations, repetitive DNA loci mutations, chromosome aberrations and micronuclei induction, neoplastic transformation in vitro, microarrays showing gene expression changes, DNA single- and double-strand breaks, biochemical analyses of enzymatic and/or non-enzymatic antioxidant defence system (Hillova and Drasil 1967; Bryant, 1975, 1976, 1979; Rieger et al., 1993; Ikushima et al., 1996; Rigaud and Moustacchi, 1996; Panda et al., 1997; Nikolova et al., 1999; Robson et al., 2000; Wang and Cai, 2000; Tiku and Kale, 2004; Venkat et al., 2001; Assis et al., 2002; Chankova and Bryant, 2002; Guo et al., 2003; Jovtchev and Stergios, 2003; Somers et al., 2004; Ulsh et al., 2004; Zhou et al., 2004; Atanasova et al., 2005; Chankova et al., 2005, 2007; Lanza et al., 2005; Biryukova et al., 2006; Chen et al., 2006; Ko et al., 2006; Otsuka et al., 2006; Bercht et al., 2007).

An adaptive response to radiation also occurs in human lymphocytes (Shadley and Wolff, 1987; Wojewózka et al., 1996; Stoilov et al., 2007). This was first demonstrated by Olivieri et al. (1984) when peripheral blood lymphocytes were irradiated with low doses of X-rays or exposed to tritium labeled thymidine and a lower than expected frequency of chromosomal aberrations was found after a subsequent higher test (or challenge) dose. However, other authors reported a diversity in response of lymphocytes; in some cases showing additive effects or no response at all (e.g. Mortazavi et al., 2003c). Sawant et al. (2001) also found an adaptive response to low dose gamma irradiation of 10T1/2 cells that were subsequently exposed to microbeam alpha-particle irradiation. Other test systems under some experimental conditions may also not show an AR (Boreham and Mitchel, 1993; Colombi and Gomes, 1997; Zasukhina et al., 2000; Pelevina et al., 2003; Joksic and Petrovic, 2004).

A popular hypothesis presented in Figure 1 postulates that the AR could be induced by reactive oxygen species (ROS) (Feinendegen et al., 1996, 1999; Jones et al., 1999; de Saint-Georges, 2004; Shankar et al., 2006). ROS are generated in organisms during metabolism and/or formed after exposure to different biotic and abiotic stimuli (UV-irradiation, ionizing radiation, ozone exposure, heavy metals), damaging some cell constituents and producing oxidative stress (Joiner et al., 1996, 1999; Mendez-Alvarez et al., 1999; Bolwell et al., 2002; Neill et al., 2002; Vranová et al., 2002; Babu et al., 2003; Asad et al., 2004; Verschooten et al., 2006; Wang et al., 2006). Ionizing radiation (IR) can damage DNA both by direct ionization and by indirect processes in which DNA is affected by numerous radiolytic reactive products. Free radicals can attack biomolecules such as DNA, proteins and lipids and initiate lipid peroxidation and generate intermediates that can react with DNA (Halliwell and Gutteridge, 1989; Marnett et al., 2003). ROS could also induce multiple localized lesions consisting in base damage, single- and double-strand breaks (SSBs and DSBs), DNA-DNA cross-links and DNA-protein cross-links (Goldberg and Lehnert, 2002; Marnett et al., 2003; Asad et al., 2004). For example, it has been found that administration of heavy metals could reduce subsequent thymus lymphocyte DNA lesions and lipid peroxidation in gamma irradiated mice (Osipov et al., 2003) and many bacteria species have adaptive responses which protect them against the toxicity and mutagenicity of DNA alkylating agents (Sedgwick and Lindahl, 2002).

 

 

Molecular mechanisms of the adaptive response

Little is currently known about the precise mechanisms of AR. There is evidence that different stress conditions can activate similar defense mechanisms in various biological systems (Joiner et al., 1996, 1999; Babu et al., 2003). The AR probably involves the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses (Figure 2): more efficient detoxification of free radicals, DNA repair systems, induction of new proteins in irradiated cells with a conditioning dose, and enhanced antioxidant production (Bryant, 1979; Wolff, 1998; Mendez-Alvarez et al., 1999; Pajovic et al., 2001; Assis et al., 2002; Chankova and Bryant, 2002; Neill et al., 2002; Sasiadek et al., 2002; Sedgwick and Lindahl, 2002; Coleman et al., 2005; Girigoswami and Ghosh, 2005; Lanza et al., 2005).

 

 

Sakamoto-Hojo et al. (2003) showed that the cell responses to ionizing radiation in lymphocytes of radiation workers involved altered expression of genes associated with cell cycle regulation, DNA repair, signal transduction, apoptosis induction/tumorigenesis and damage response/ maintenance of genetic stability (P53-related functions). Similar results were obtained for human lymphoblastoid cells in vitro and the authors proposed that certain low dose-induced alterations in cellular functions could be predictive of the subsequent genomic damage risk (Coleman et al., 2005). Other recent molecular studies suggested that alternative dose-specific pathways of radioadaptive response could exist in mammalian cells: one response activated at low doses by the protein kinase C through p38 MAP kinase resulting in P53 activation and another activated at higher doses resulting in activation of ERK and JNK kinases and WIP phosphatase (Lanza et al., 2005). AR is known to require a certain minimal dose for activation (Leonard, 2007). Low levels of damage could be triggering events that signal the activation of DNA repair systems (Boreham and Mitchel, 1991; Wolff, 1998; Matsumoto et al., 2004). For example, the persistence of DNA strand discontinuities could serve as a triggering signal for the adaptation of human lymphocytes against ionizing radiation exposure (Stoilov et al., 2007). The magnitude of the AR has been shown to increase with the dose of radiation up to a certain threshold (Bryant, 1976). A specific dose of UVB was required to induce AR in Euglena (Takahashi et al., 2006). Induction of AR by methylating agents has been reported in eukaryotic cells as well. For example, Mahmood et al. (1996) reported that in murine cells the AR was induced by the methylating agent methyl methanesulfonate and was stronger than that induced by the ethylating agent ethyl methanesulfonate. Schlade-Bartusiak et al. (2002) showed a more pronounced AR in human lymphocytes after treatment with bleomycin, which generates DNA breaks, than with the alkylating agent mitomycin.

Experiments with restriction enzymes indicated that DNA DSBs with blunt or cohesive ends were capable of inducing an AR (Wolff, 1996, 1998). Some radiosensitive DSB repair-deficient mutants were found to exhibit no induced radioresistance, suggesting the involvement of DSB rejoining (Skov et al., 1994). Changes in chromatin conformation could result in less sensitivity of chromatin to damage by indirect effect of a test dose or in increased accessibility of damaged sites to repair enzymes (Belyaev et al., 1996; Kleczkowska and Althaus, 1996). Experiments with repair inhibitors suggested that poly-ADP-Ribose Polymerase-1 (PARP) is also involved in the AR (Kleczkowska and Althaus, 1996; Wolff, 1998; Marples and Joiner, 2000; Patra et al., 2003) possibly interfering in the cell cycle control (Tang et al., 2005) or in the damage-sensing process (Marples et al., 2004). This was confirmed and it has been postulated that the AR can be interpreted in terms of increased non-homologous end-joining of DSB or increased homologous recombination (Vaganay-Juery et al., 2000; Marples et al., 2004; Raaphorst et al., 2006). On the other hand PARP may not be involved in the induction of AR after treatment with alkylating agents in mouse bone marrow cells (Guruprasad et al., 2002). An AR was found to be absent in some radiosensitive tumor lines and ataxia telangiectasia patients cells (Lambin et al., 1994). In our experiments the highly radioresistant Chlamydomonas reinhardtii strain H-3 surprisingly showed a clear adaptive response (Figure 3). These results show that the already enhanced ability of strain H-3 to repair radiation damage, evidenced by its radioresistance to single doses of radiation, does not prevent this strain from ‘adapting’ still further following a priming dose of radiation (Chankova et al., 2005). In contrast, the level of AR from Bloom syndrome (human autosomal recessive disorder, characterized by chromosomal instability and increased risk of malignancy at an early age) patients blood cells has been shown to be the same as that in control cells from healthy donors (Zasukhina et al., 2000). The hamster cell line EM9, which is SSB repair-deficient, can also develop an AR (Skov et al., 1994). CHO cells mutated for different components of the nucleotide excision repair pathway do not express mutation and/or survival AR (Hafer et al., 2007). In spite of the variation in AR in different systems, it has been postulated that AR analysis could be used for assaying DNA repair capacity (Sasiadek et al., 2002). It has also been suggested that membrane damage may switch on some of these responses (Skov et al., 1994) and/or be reduced as a result of AR (Girigoswami and Ghosh, 2005; El-Tayeb et al., 2006).

 

 

Does the AR operate via up-regulation of DNA repair?

DNA damage due to hydroxyl radicals derived from the radiolytic decomposition of H2O produces lesions that strongly induce DNA repair mechanisms (Boreham and Mitchel, 1991). Experiments in various biological systems have been performed to test the hypothesis that DNA repair up-regulation could be involved in the AR. There is evidence that DNA repair underlies the AR induced by low radiation doses in human and plant cells (Lambin et al, 1994; Patra et al., 2003) by increasing the amount and rate of DNA repair (Joiner et al., 1996; Joiner et al., 1999). For example, when peripheral blood mononuclear cells from residents of Ramsar (a high natural background radiation area) were irradiated with a challenging dose of gamma rays, Mohammadi et al. (2006) detected lower levels of micronuclei, higher numbers of apoptotic cells and enhanced DNA repair. It has been proposed that these effects could be related to the induction of an AR. The AR induced by conditioning UVB exposures in Euglena may not be due to biosynthetic UV-absorbing compounds, but to the induction of photolyase enzymes (Takahashi et al., 2006). Activation of UVB-induced AR in human skin cells could involve a p53-dependent gene program with p53-induced cell cycle arrest and DNA repair (Decraene et al., 2005). The study of repair kinetics of DNA damage in Chinese hamster V79 cells showed that the radioadaptive response could be a result of DNA repair mechanisms which lead to less residual DNA damage, but not from the induction of protective mechanisms that reduce the initial DNA damage (Ikushima et al., 1996). An adaptive response was observed through micronuclei formation and neoplastic transformation in murine 10T1/2 cells and the authors postulated that this adaptive response resulted from an enhanced DSB repair (Azzam et al., 1994). This would be in agreement with our finding of accelerated DSB rejoining in C. reinhardtii following a conditioning dose of gamma rays (Chankova and Bryant, 2002) or radiomimetics (Chankova et al., 2007) presented in Figures 4 and 5. A reduction in deletion-type mutants in adapted cells may also be a result of DSB DNA repair in various cell systems (Rigaud and Moustacchi, 1996).

 

 

 

 

However, as Szumiel (2005) pointed out, the view that DNA repair is stimulated in the ‘primed’ and challenged cell is not supported by all the available data. For instance, at least in some cases the AR may have no connection with modification of repair processes (Tskhovrebova and Makedonov, 2004). In such cases, the AR could be partly due to diminished fixation of DSBs (Szumiel, 2005). For example, induction of AR has been observed in terms of reduced initial DNA damage as well, which could be due to increased oxidative defense processes or to other undefined molecular processes, e.g. perturbation of cell cycle progression (Atanasova et al., 2005; Cramers et al., 2005).

Some evidence indicates that the H2O2 induced AR in cultured human retinal pigment epithelium (RPE) cells involves increased nuclear DNA protection but no adaptive benefit for mtDNA protection or repair (Jarrett and Boulton, 2005). Hence, it has been suggested that the AR could be an important antioxidant defense for cells located in inherently oxidizing microenvironments. However, mitochondria have been viewed as a weak link in this defense mechanism which would contribute to aging and age-related disease (Jarrett and Boulton, 2005).

 

Does the AR involve induction of new proteins synthesis?

Little is known about the proteins and genes involved in adaptive responses in cells. Changes in gene transcriptional levels have been found after exposure to ionizing radiation with low doses that result in the induction of AR (Wolff, 1998; Coleman et al., 2005; Lanza et al., 2005). A clue as to the nature of the underlying process was provided by results showing a dependence on de novo protein synthesis. Treatment of Oedogonium, Chlamydomonas and Closterium cells with protein synthesis inhibitors (cycloheximide and chloramphenicol) after the first ‘conditioning’ dose prevented the induced repair responses in these organisms (Horsley and Lazlo, 1971; Bryant, 1975; Howard and Cowie, 1978; Chankova and Bryant, 2002). The synthesis of DNA-binding proteins (MWs 50, 74 and 130 kdal) was found in radiation-conditioned cells of C. reinhardtii (Bryant, 1979). Our previous work showed an up-regulation of DNA DSB rejoining four hours after irradiation of C. reinhardtii CW15 (a Cell-Wall-less mutant with WT radiation response) that was strongly reduced when cells were treated with the protein synthesis inhibitors cycloheximide and chloramphenicol (Chankova and Bryant, 2002) (Figure 6).

 

 

The induction of new protein synthesis by low doses could be caused by an effect of low doses on chromatin conformation near genes coding for DNA repair proteins (Belyaev et al., 1996). The AR to alkylating agents in Escherichia coli is thought to be related to an increased expression of genes which encode DNA repair proteins (aidB, ada, alkA, alkB) (Rohankhedkar et al., 2006). The AidB component of E. coli AR to alkylating agents has been identified as a flavin-containing DNA-binding protein and has been predicted to catalyze the direct repair of alkylated DNA (Rohankhedkar et al., 2006).

Robson et al. (1999) isolated a novel gene from L132 cells that is down-regulated in response to ionizing radiation (DIR1 gene) which they postulated played a regulatory role in the AR. Later research on cells showing low-dose hypersensitivity (V79, RT112 and UM-UC-3) showed that antisense oligonucleotides against the DIR1 gene resulted in an increased rate of rejoining of DNA single-strand breaks coupled with an increase in cell survival after a dose of 2Gy (Robson et al., 2000). However, ataxia telangiectasia cells (ATBIVA), which do not show low-dose hypersensitivity, did not show such enhanced repair and survival. The authors concluded that radiosensitive cells such as those from AT patients lack the ability to switch on the DIR1 gene. Not all examples of induced AR involve de novo protein synthesis. For example, there are earlier observations that hydrogen peroxide induced a cross-adaptive response to cumene hydroperoxide in E. coli which did not require novel gene products but involved modification of the small subunit of Ahp, a protein involved in the protection against alkyl hydroperoxides (Asad et al., 1998).

 

Could activation of antioxidant systems have a role in induced resistance?

Mendez-Alvarez et al. (1999) proposed that the cell ability to induce AR could be affected by altering cellular oxidative stress levels. Enzymes are considered as a very important component of cell defense mechanisms which protect organisms from the harmful action of ROS damaging DNA and other biomolecules. It is assumed that enzymatic, non-enzymatic and indirect antioxidant defense systems could be involved in the formation of AR to oxidative stress (Mendez-Alvarez et al., 1999; Chen et al., 2006; Yan et al., 2006; Tosello et al., 2007). Joksic et al. (2000) suggested that oxidative stress can trigger an antioxidant response that includes changes in the activity of enzymatic defense system, mainly SOD. Radioresistant variants isolated from MCF-7 human carcinoma cells following fractionated radiation or overexpression of MnSOD demonstrated dose-modified factors at 10% isosurvival (Guo et al., 2003). The authors speculated that maybe the induction of MnSOD after fractionated doses caused a redox alteration that resulted in the up-regulation of stress response genes and radiation induced AR. Similarly, enhancement of the antioxidative capacities (catalase and MnSOD) probably played an important role in the reduction of initial DNA damage by low-dose-rate radiation in mice spleen (Otsuka et al., 2006). DNA microarray analysis has revealed that GPX1, CAT, SOD1 and several other genes involved in peroxidase activity were up-regulated after low-dose X-ray exposure of HUVEC cells (Lanza et al., 2005). The AR of yeast cells induced by the oxidants H2O2, menadione and juglone was associated with an increase in the activity of cellular catalase, SOD, glucose-6-phosphate dehydrogenase, and glutathione reductase, the main enzymes involved in cell defense against oxidative stress (Biryukova et al., 2006). Enhancement of these antioxidant activities could be involved in menadione-induced AR to menadione and to H2O2 in Bacillus sp. F26 (Yan et al., 2006). Leisinger et al. (1999) described a glutathione peroxidase homologous gene in Chlamydomonas reinhardtii whose expression is up-regulated after treatment with different oxidative stress inducing agents (Leisinger et al., 2001). Other studies indicated that some non-enzymatic antioxidants could affect the AR through binding and detoxification of the genotoxic chemical. For example, it has been recently demonstrated that the AR induced by sublethal concentrations of some oxisterols and prostaglandins in PC12 cells is mediated through elevation of cellular glutathione contents (Chen et al., 2006). Similarly, pretreatment of murine and human cells with alkylating or 8-oxoG inducing agents prior to a test dose resulted in a twofold shift of cellular glutathione levels as an AR (Bercht et al., 2007). Chlamydomonas reinhardtii has been reported to produce metal-binding peptides in response to stress induced by different heavy metals (Cd, Hg, Ag) (Howe and Merchant, 1992) and the cadmium-induced AR in Allium cepa was prevented after inhibition of phytochelatin synthesis (Panda et al., 1997). Similarly, inhibition of metallothionein synthesis prevented the AR after heavy metal (Cu, Pb) conditioning treatment in Vicia faba (Rieger et al., 1993). Inhibition of cytoplasmic protein synthesis prevented the AR induced by Cd in Allium cepa (Panda et al., 1997). Inhibition of de novo protein synthesis by cycloheximide probably inhibited the Cu2+-dependent metallothionein synthesis in human peripheral blood lymphocytes thereby eliminating the AR triggered by copper sulphate (Nikolova et al., 1999).

On the other hand, ROS (e.g. hydrogen peroxide and nitric oxide) could serve as signal transducers in plant and animal cells (Neill et al., 2002; Vranová et al., 2002; Babu et al., 2003; Matsumoto et al., 2004). As signaling molecules, ROS might affect the development of AR through participation in the damage-sensing process after conditioning dose exposure. For example, in UV-irradiation experiments with human skin fibroblasts the addition of antioxidants reduced the cellular oxidative stress and adaptive response in a concentration-dependent manner (Jones et al., 1999). Thus, it is possible that in some cases the increased scavenging of ROS by the antioxidant system might reduce the induced damage resulting in AR. The contribution of the antioxidant system for the development of AR could be further complicated by the fact that certain ROS are known to serve as signal transducers in plant and animal cells.

Miura (2004) showed an insignificantly increased level of the activity of CAT, GPx, GR and glutathione content after low dose and subsequently given higher dose of X-rays irradiation in rat glial cells. He therefore concluded that antioxidant defense can contribute only partly to the radiation induced AR in tested cells. The AR in fibroblasts derived from transgenic mice overexpressing the Cu/ZnSOD gene appeared to be unrelated to the amount of SOD in the cells and, hence, independent of superoxide radicals (Wolff, 1996).

 

Kinetics of the adaptive response

As summarized by Feinendegen (2005), adaptive protection develops with a delay of hours, may last for days to months, decreases steadily at doses above about 100 mGy to 200 mGy and is not observed anymore after acute exposures to more than 500 mGy. Indeed, there is abundant evidence that the adaptive response depends on the experimental design. The adaptive response was shown to be both dose and time-dependent with a maximal effect occurring several hours later, for example between four to six hours after exposure for the unicellular green alga Chlamydomonas reinhardtii (Bryant, 1976; Chankova et al., 2005, 2007). The experimental design used by us for induction of AR by different genotoxic agents in the green alga Chlamydomonas reinhardtii as a test system is shown in Figure 7. We also observed a dose-dependence of the radiation-induced AR in C. reinhardtii when DSB DNA rejoining was used as an indicator (Chankova and Bryant, 2002). A small conditioning dose of gamma rays irradiation led to a small increase in the rate of DSB rejoining but when the magnitude of the conditioning dose was progressively increased there was a corresponding decrease in the fraction of damage remaining (Figure 8). Heat shock protection against induction of chromatid aberrations by clastogens in Vicia faba was found to be dependent on the time span (from less than ten minutes up to four hours) between the test dose and the adaptive treatment (Rieger and Michaelis, 1988). The time course of the adaptive response in lymphocytes was found to be similar to that in plant systems, reaching a plateau after about six hours (Shadley and Wolff, 1987). In murine leukocytes the minimum adaptive dose lies between 0.005 and 0.01 Gy of gamma rays and the early AR to a test dose of 1.0 Gy is induced as early as 30 min after the exposure and persists for at least 18 h (Morales-Ramírez and Mendiola-Cruz, 2004). Venkat et al. (2001) observed a maximum AR when a test dose of 100 cGy was given four hours after an adaptive dose, 30 h following the mitogenic stimulation of lymphocytes. The protective effect against N-methyl-N’-nitro-N-nitrosoguanidine induced by prior treatment with H2O2 in E. coli is also time dependent, decreasing 15 min after the pretreatment and almost abolished after 30 min (Asad et al., 1997).

 

 

 

 

Besides being brief, the AR to irradiation could also be modulated (Joiner et al., 1996, 1999; Raaphorst et al., 2000; Tiku and Kale, 2004), e.g. AR could be induced more effectively when a conditioning dose was given in small fractions (Tiku and Kale, 2004). It has been proposed that such fractionated irradiation of human fibroblasts could result in elevated survival due to repair of sublethal damage (Raaphorst et al., 2000). The efficiency of cellular defense reactions that are activated can vary and depend on the level and type of the impact. It has been more recently reported that in some instances the conditioning dose can act synergistically, thereby increasing the frequency of chromosomal aberrations seen following the test dose (Matsumoto et al., 2004; Zhou et al., 2004). Different agents may have different impacts which could result in adaptive reactions of variable efficiency (Boreham and Mitchel, 1991; Marples and Joiner, 1993; Joiner, 1994; Schlade-Bartusiak et al., 2002; Marples et al., 2004; Matsumoto et al., 2004). For example, acute doses of alpha-particles and other high Linear Energy Transfer (LET) radiations, such as neutrons, appear to be less efficient in eliciting an adaptive response than low LET radiations (e.g. X-rays) (Boreham and Mitchel, 1991; Marples and Joiner, 1993; Joiner, 1994) presumably since the level of local DNA damage is more severe and therefore immediately activates the G2 sensing systems (Marples et al., 2004). However, some reports indicated that AR following neutron exposure could be observed in V79 Chinese hamster cells (Marples and Skov, 1996) or human lymphocytes in vitro (Gajendiran et al., 2001).

Remarkably, it has recently been reported that in prostate cells of pKZ1 transgenic mice X-ray-induced ‘reverse’ AR could be observed when the high damaging dose preceded the low dose (Day et al., 2007). This ‘reverse’ AR was of similar magnitude to the AR observed when the low dose was given first. These results may indicate that the mechanisms underlying AR may not be due to prevention of damage induced by the high dose but to modulation of the cellular response to this damage.

 

Relevance of the adaptive response

Low-dose radiation may have some beneficial effects, e.g. adaptive protection causing DNA damage prevention and repair and immune stimulation (Upton , 2001; Liu, 2003; Ghiassi-nejad et al., 2004; Feinendegen, 2005). Low to intermediate doses of ionizing radiation have been observed to enhance growth and survival, augment the immune response, and increase resistance to the mutagenic and clastogenic effects of further irradiation in plants, bacteria, insects and mammals (Upton, 2001). Stimulation of immunity has been observed in human populations after long-term exposure to high level natural background radiation (Ghiassi-nejad et al., 2004). Ghiassi-nejad et al. (2004) observed a significant increase of CD69 expression on TCD4+ stimulated cells and a significant increase of total serum IgE in Ramsar residents. Removal of damaged cells occurred in vivo by way of a low dose-induced immune competence (reviewed in Feinendegen, 2005). Nevertheless, some scientists argue that the AR does not appear to be a relevant mechanism for radiation protection because the worst outcome for the cell (cell death) is probably the best outcome for the organism as a whole since the low (conditioning) dose could also generate a risk of cellular transformation (Hofseth, 2004; de Saint-Georges, 2004). Indeed, there is abundant experimental evidence that chronic low-dose occupational exposure to ionizing radiation could result in adverse health effects (Lin and Mao, 2004) and increased DNA damage (Joksic and Spasojevic-Tisma, 1998; Cardoso et al., 2001; Maffei et al., 2002; Sari-Minodier et al., 2002; Hadjidekova et al., 2003; Zakeri and Assaei, 2004; Güerci et al., 2006; Sari-Minodier et al., 2007). Similarly, increased levels of DNA damage have been obtained for chromium platers (Benova et al., 2002), offset printing workers (Aksoy et al., 2005), welders (Iarmarcovai et al., 2005; 2007), pathologists/anatomists exposed to formaldehyde (Iarmarcovai et al., 2007), and patients taking certain phytopharmaceuticals (Lazutka and Mierauskiene, 2001) or after long-term low-dose antimicrobial prophylaxis (Slapyte et al., 2002). An increased frequency of micronuclei has also been detected after in vitro irradiation of domestic animals lymphocytes (Danika and Dunja, 2007) but not in the lymphocytes of cattle raised in the vicinity of a nuclear power plant (Lee et al., 2007). Conversely, very low-dose rate chronic gamma irradiation induced a marked cytogenetic adaptive response to a subsequent higher dose in mouse germ cells and probably did not cause any risk of damaging effects to the offspring of the irradiated male animals (Cai and Wang, 1995).

Some authors consider that it is misleading to conceive the AR in terms of radioprotection because the AR is highly dependent on the genetic constitution and its measurement depends on the experimental design (Salone et al., 1996). For instance, the genotoxic effect of radiation in occupationally exposed persons may or may not vary depending on alcohol consumption, age and gender (Maffei et al., 2002; Hadjidekova et al., 2003; Zakeri and Assaei, 2004; Iarmarcovai et al., 2007; Sari-Minodier et al., 2007). The increased frequencies of chromosomal aberrations and sister chromatid exchanges in radiation workers could indicate a cumulative effect of low level chronic exposure to ionizing radiation, pointing to the relevance of conducting cytogenetic analysis in addition to physical dosimetry in such cases (Cardoso et al., 2001). Although cytokinetic and cytostatic effects have been detected in heavy and moderate smokers (Calderón-Ezquerro et al., 2007), smoking habits may or may not affect the genotoxic effect of chronic radiation exposure (Maffei et al., 2002; Hadjidekova et al., 2003; Sari-Minodier et al., 2007).

Nevertheless, a better understanding of the molecular mechanisms underlying the AR may lead to an improvement in radiation protection, e.g. of astronauts during long-term space flights, risk assessment and management, and cancer treatment strategies (Delone et al., 1991; Wang and Cai, 2000; Upton, 2001; Takahashi et al., 2002; Bonner, 2003; Mortazavi et al., 2003a, 2003b; Liu, 2003; Schaffer et al., 2004; Preston, 2005). In preliminary cytogenetic studies, after in vitro irradiation with a test dose of gamma rays, a strong cytogenetic AR was induced in the lymphocytes of residents of the very high background radiation areas of Ramsar (Ghiassi-nejad et al., 2002). A study of the residents living in radioactively contaminated buildings in Taiwan suggested that chronic irradiation could actually be an effective prophylaxis against cancer (Chen et al., 2004). In support of this idea, lifelong low-dose irradiation accompanied by immune activation was shown to result in suppression of thymic lymphoma induction in mice (Ina et al., 2005). Low-dose irradiation has been used successfully for cancer therapy without causing significant symptoms or presenting significant risk (Cuttler and Pollycove, 2003). In line with these observations, some authors proposed additional coefficients reflecting the protective role of low-dose radiation to be introduced in the mathematical dose-response model for estimation of radiation risk (Scott, 2004; Feinendegen and Neumann, 2006).

In conclusion, a better understanding of AR could open up new approaches for protection of cells. The AR and the ability to modify it may play important roles in fractionated radiotherapy and can help to verify whether this phenomenon affects the estimation of the risk of low level radiation exposure. In order to more fully understand the AR, at least two hypothesis need to be tested: firstly, that radiation-induced AR may differ depending on the cell type and genotype; and secondly, that altering cellular oxidative stress levels have an impact on the ability of the cells to initiate the AR.

 

Acknowledgments

This work was supported by the Bulgarian Ministry of Education and Science (project K-1204 and project BioCORE), St Andrews University, The Royal Society, UK and the Bulgarian Academy of Sciences.

 

References

Aksoy H, Yõlmaz S, Çelik M, Yüzbaolu D and Ünal F (2005) Genotoxicity study in lymphocytes of offset printing workers. J Appl Toxicol 26:10-15.         [ Links ]

Asad LM, Asad NR, Silva AB, Felzenszwalb I and Leitão AC (1997) Hydrogen peroxide induces protection against N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) effects in Escherichia coli. Mutat Res 383:137-142.         [ Links ]

Asad NR, Asad LM, Silva AB, Felzenszwalb I and Leitão AC (1998) Hydrogen peroxide induces protection against lethal effects of cumene hydroperoxide in Escherichia coli cells: An Ahp dependent and OxyR independent system? Mutat Res 407:253-259.         [ Links ]

Asad NR, Asad LMBO, de Almeida CEB, Felzenszwalb I, Cabral-Neto JB and Leitão AC (2004) Several pathways of hydrogen peroxide action that damage the E. coli genome. Genet Mol Biol 27:291-303.         [ Links ]

Assis ML, De Mattos JC, Caceres MR, Dantas FJ, Asad LM, Asad NR, Bezerra RJ, Caldeira-de-Araujo A and Bernardo-Filho M (2002) Adaptive response to H2O2 protects against SnCl2 damage: The OxyR system involvement. Biochimie 84:291-294.         [ Links ]

Atanasova P, Hadjidekova V and Darroudi F (2005) Influence of conditioning on cell survival and initial chromosome damage in X-irradiated human cells. Trakia J Sci 3:37-42.         [ Links ]

Azzam EI, Raaphorst GP and Mitchel RE (1994) Radiation-induced adaptive response for protection against micronucleus formation and neoplastic transformation in C3H 10T1/2 mouse embryo cells. Radiat Res 138:S28-31.         [ Links ]

Babu ST, Akhtar TA, Lampi MA, Tripuranthakam S, Dixon GD and Greenberg BM (2003) Similar stress responses are elicited by copper and ultraviolet radiation in the aquatic plant Lemna gibba: Implication of reactive oxygen species as common signals. Plant Cell Physiol 44:1320-1329.         [ Links ]

Belyaev IY, Spivak IM, Kolman A and Harms-Ringdahl M (1996) Relationship between radiation induced adaptive response in human fibroblasts and changes in chromatin conformation. Mutat Res 358:223-230.         [ Links ]

Benova D, Hadjidekova V, Hristova R, Nikolova T, Boulanova M, Georgieva I, Grigorova M, Popov T, Panev T, Georgieva R, et al. (2002) Cytogenetic effects of hexavalent chromium in Bulgarian chromium platers. Mutat Res 514:29-38.         [ Links ]

Biryukova EN, Medentsev AG, Arinbasarova AYu and Akimenko VK (2006) Tolerance of the yeast Yarrowia lipolytica to oxidative stress - Article in Russian. Mikrobiologiia. 75:293-298.         [ Links ]

Bolwell PG, Bindschedler LV, Blee KA, Butt VS, Davies DR, Gardner SL, Gerrish C and Minibayeva F (2002) The apoplastic oxidative burst in response to biotic stress in plants: A three-component system. J Exp Bot 53:1367-1376.         [ Links ]

Bonner WM (2003) Low-dose radiation: Thresholds, bystander effects, and adaptive responses. Proc Natl Acad Sci USA 100:4973-4975.         [ Links ]

Boreham DR and Mitchel RE (1991) DNA lesions that signal the induction of radioresistance and DNA repair in yeast. Radiat Res 128:19-28.         [ Links ]

Boreham DR and Mitchel REJ (1993) DNA repair in Chlamydomonas reinhardtii induced by heat shock and gamma radiation. Radiat Res 135:365-371.         [ Links ]

Bercht M, Flohr-Beckhaus C, Osterod M, Rünger TM, Radicella JP and Epe B (2007) Is the repair of oxidative DNA base modifications inducible by a preceding DNA damage induction? DNA Repair 6:367-373.         [ Links ]

Bryant PE (1974) Change in sensitivity of cells after split dose recovery a further test of the repair hypothesis. Int J Radiat Biol 26:499-504.         [ Links ]

Bryant PE (1975) Decrease in sensitivity of cells after split-dose recovery: Evidence for the involvement of protein synthesis. Int J Radiat Biol 27:95-102.         [ Links ]

Bryant PE (1976) Absence of oxygen effect for induction of resistance to ionising radiation. Nature 261:588-590.         [ Links ]

Bryant PE (1979) Evidence for inducible DNA-associated proteins formed during the development of increased resistance to radiation in Chlamydomonas. Prog Phys Theor Chem 6:305-313.         [ Links ]

Cai L and Wang P (1995) Induction of cytogenetic adaptive response in germ cells of irradiated mice with very low-dose rate of chronic g-irradiation and its biological influence on radiation-induced DNA or chromosomal damage and cell killing in their male offspring. Mutagenesis 10:95-100.         [ Links ]

Calderón-Ezquerro C, Sánchez-Reyes A, Sansores RH, Villalobos-Pietrini R, Amador-Muñoz O, Guerrero-Guerra C, Calderón-Segura ME, Uribe-Hernández R and Gómez-Arroyo S (2007) Cell proliferation kinetics and genotoxicity in lymphocytes of smokers living in Mexico city. Hum Exp Toxicol 26:715-722.         [ Links ]

Cardoso RS, Hakahashi-Hyodo S, Peitl Jr P, Ghilardi-Neto T and Sakamoto-Hojo ET (2001) Evaluation of chromosomal aberrations, micronuclei, and sister chromatid exchanges in hospital workers chronically exposed to ionizing radiation. Terratog Carcinog Mutagen 21:431-439.         [ Links ]

Chankova SG and Bryant PE (2002) Acceleration of DNA-double strand rejoining during the adaptive response of Chlamydomonas reinhardtii. Radiat Biol Radioecol 42:600-603.         [ Links ]

Chankova GS, Matos JA, Simões F and Bryant PE (2005) Adaptive response of a new radioresistant strain of Chlamydomonas reinhardtii and correlation with increased DNA double-strand break rejoining. Int J Radiat Biol 81:509-514.         [ Links ]

Chankova SG, Dimova E, Dimitrova M and Bryant PE (2007) Induction of DNA double-strand breaks by zeocin in Chlamydomonas reinhardtii and the role of increased DNA double-strand breaks rejoining in the formation of an adaptive response. Radiat Environ Biophys 46:409-416.         [ Links ]

Chen WL, Luan YC, Shieh MC, Chen ST, Kung HT, Soong KL, Yeh YC, Chou TS, Mong SH, Wu JT, et al. (2004) Is chronic radiation an effective prophylaxis against cancer? J Am Phys Surg 9:6-10.         [ Links ]

Chen ZH, Yoshida Y, Saito Y, Sekine A, Noguchi N and Niki E (2006) Induction of adaptive response and enhancement of PC12 cell tolerance by 7-hydroxycholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms. J Biol Chem 281:14440-14445.         [ Links ]

Coleman MA, Yin E, Peterson LE, Nelson D, Sorensen K, Tuckera JD and Wyrobeka AJ (2005) Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response. Radiat Res 164:369-382.         [ Links ]

Colombi D and Gomes SL (1997) An alkB gene homolog is differentially transcribed during the Caulobacter crescentus cell cycle. J Bacteriol 179:3139-3145.         [ Links ]

Cramers P, Atanasova P, Vrolijk H, Darroudi F, van Zeeland AA, Huiskamp R, Mullenders LH and Kleinjans JC (2005) Pre-exposure to low doses: Modulation of X-ray-induced DNA damage and repair? Radiat Res 164:383-390.         [ Links ]

Cuttler JM and Pollycove M (2003) Can cancer be treated with low doses of radiation? J Am Phys Surg 8:108-111.         [ Links ]

Danika H and Dunja R (2007) Micronuclei in lymphocytes of horses and pigs after in vitro irradiation. Acta Vet 57:341-350.         [ Links ]

Day TK, Zeng G, Hooker AM, Bhat M, Scott BR, Turner DR and Sykes PJ (2007) Adaptive response for chromosomal inversions in pKZ1 mouse prostate induced by low doses of X radiation delivered after a high dose. Radiat Res 167:682-692.         [ Links ]

Decraene D, Smaers K, Maes D, Matsui M, Declercq L and Garmyn M (2005) A low UVB dose, with the potential to trigger a protective p53-dependent gene program, increases the resilience of keratinocytes against future UVB insults. J Invest Dermatol 125:1026-1031.         [ Links ]

Delone NL, Voronkov IUI, Solonichenko VG and Antipov VV (1991) Genetic aspects of man’s adaptation to long-term space flight - In Russian. Kosm Biol Aviakosm Med 25:10-15.         [ Links ]

El-Tayeb M, El-Enany A and Ahmed N (2006) Salicylic acid-induced adaptive response to copper stress in sunflower (Helianthus annuus L.). Plant Growth Reg 50:191-199.         [ Links ]

Feinendegen LE (2005) Evidence for beneficial low level radiation effects and radiation hormesis. Br J Radiobiol 78:3-7.         [ Links ]

Feinendegen LE, Bond VP, Sondhaus CA and Muehlensiepen H (1996) Radiation effects induced by low doses in complex tissue and their relation to cellular adaptive responses. Mutat Res 358:199-205.         [ Links ]

Feinendegen LE, Bond VP, Sondhaus CA and Altman KI (1999) Cellular signal adaptation with damage control at low doses vs. the predominance of DNA damage at high doses. C R Acad Sci III 322:245-251.         [ Links ]

Feinendegen LE and Neumann RD (2006) The issue of risk in complex adaptive systems: The case of low-dose radiation induced cancer. Hum Exp Toxicol 25:11-17.         [ Links ]

Friesner JD, Liu B, Culligan K and Britt AB (2005) Ionizing radiation-dependent g-H2AX focus formation requires ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related. Mol Biol Cell 16:2566-2576.         [ Links ]

Gajendiran N and Jeevanram RK (2002) Environmental radiation as the conditioning factor for the survival of yeast Saccharomyces cerevisiae. Indian J Exp Biol 40:95-100.         [ Links ]

Gajendiran N, Tanaka K, Kumaravel TS and Kamada N (2001) Neutron-induced adaptive response studied in Go human lymphocytes using the comet assay. J Radiat Res 42:91-101.         [ Links ]

Ghiassi-Nejad M, Mortazavi SMJ, Cameron JR, Niroomand-rad A and Karam PA (2002) Very high background radiation areas of Ramsar, Iran: Preliminary biological studies. Health Physics 82:87-93.         [ Links ]

Ghiassi-nejad M, Zakeri F, Assaei RGh and Kariminia A (2004) Long-term immune and cytogenetic effects of high level natural radiation on Ramsar inhabitants in Iran. J Environ Radioact 74:107-116.         [ Links ]

Girigoswami BK and Ghosh R (2005) Response to gamma-irradiation in V79 cells conditioned by repeated treatment with low doses of hydrogen peroxide. Radiat Environ Biophys 44:131-137.         [ Links ]

Goldberg Z and Lehnert BE (2002) Radiation-induced effects in unirradiated cells: A review and implications in cancer. Int J Oncol 21:337-349.         [ Links ]

Güerci AM, Grillo CA, Dulout FN and Seoane AI (2006) Assessment of genotoxic damage in lymphocytes of hospital workers exposed to ionizing radiation in Argentina. Arch Environ Occup Health 61:163-169.         [ Links ]

Guo G, Yan-Sanders Y, Lyn-Cook BD, Wang T, Tamae D, Ogi J, Khaletskiy A, Li Z, Weydert C, Longmate JA, et al. (2003) Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses. Mol Cell Biol 23:2362-2378.         [ Links ]

Guruprasad KP, Vasudov V, Anilkumar MN and Chethan SA (2002) Inducible protective processes in animal systems. X. Influence of nicotinamide in methyl methanesulphonate-adapted mouse bone marrow cells. Mutagenesis 17:108.         [ Links ]

Hadjidekova VB, Bulanova M, Bonassi S and Neri M (2003) Micronucleus frequency is increased in peripheral blood lymphocytes of muclear power plant workers. Radiat Res 160:684-690.         [ Links ]

Hafer K, Iwamoto KK, Scuric Z and Schiestl RH (2007) Adaptive response to gamma radiation in mammalian cells proficient and deficient in components of nucleotide excision repair. Radiat Res 168:168-174.         [ Links ]

Halliwell B and Gutteridge JM (1989) Free radicals in Biology and Medicine. 2nd ed. Clarendon Press, Oxford, pp 1-543.         [ Links ]

Hillova J and Drasil V (1967) The inhibitory effect of iodoacetamide on recovery from sub-lethal damage in Chlamydomonas reinhardti. Int J Radiat Biol Relat Stud Phys Chem Med 12:201-208.         [ Links ]

Hofseth LJ (2004) The adaptive imbalance to genotoxic stress: Genome guardians rear their ugly heads. Carcinogenesis 25:1787-1793.         [ Links ]

Horsley RJ and Laszlo A (1971) Unexpected additional recovery following a first X-ray dose to a synchronous cell culture. Int J Radiat Biol Relat Stud Phys Chem Med 20:593-596.         [ Links ]

Horsley RJ and Laszlo A (1973) Additional recovery in X-irradiated Oedogonium cardiacum can be suppressed by cycloheximide. Int J Radiat Biol Relat Stud Phys Chem Med 23:201-204.         [ Links ]

Howard A and Cowie FG (1976) Induced resistance in a desmid Closterium moniliferum. Radiat Res 65:540-549.         [ Links ]

Howard A and Cowie FG (1978) Induced resistance in Closterium: Indirect evidence for the induction of repair enzyme. Radiat Res 75:607-616.         [ Links ]

Howe G and Merchant S (1992) Heavy metal-activated synthesis of peptides in Chlamydomonas reinhardtii. Plant Physiol 98:127-136.         [ Links ]

Iarmarcovai G, Sari-Minodier I, Chaspoul F, Botta C, De Mèo M, Orsière T, Bergé-Lefranc JL, Gallice P and Botta A (2005) Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1 and XRCC3 polymorphisms. Mutagenesis 20:425-432.         [ Links ]

Iarmarcovai G, Bonassi S, Sari-Minodier I, Baciuchka-Palmaro M, Botta A and Orsière T (2007) Exposure to genotoxic agents, host factors, and lifestyle influence the number of centromeric signals in micronuclei: A pooled re-analysis. Mutat Res 615:18-27.         [ Links ]

Ikushima T, Aritomi H and Morisita J (1996) Radioadaptive response: Efficient repair of radiation-induced DNA damage in adapted cells. Mutat Res 358:193-198.         [ Links ]

Ina Y, Tanooka H, Yamada T and Sakai K (2005) Suppression of thymic lymphoma induction by life-long low-dose-rate irradiation accompanied by immune activation in C57BL/6 mice. Radiat Res 163:153-158.         [ Links ]

Jarrett SG and Boulton ME (2005) Antioxidant up-regulation and increased nuclear DNA protection play key roles in adaptation to oxidative stress in epithelial cells. Free Radic Biol Med 38:1382-1391.         [ Links ]

Joiner MC (1994) Induced radioresistance: An overview and historical perspective. Int J Radiat Biol 65:79-84.         [ Links ]

Joiner MC, Lambin P, Malaise EP, Robson T, Arrand JE, Skov KA and Marples B (1996) Hypersensitivity to very-low single radiation doses: Its relationship to the adaptive response and induced radioresistance. Mutat Res 358:171-183.         [ Links ]

Joiner MC, Lambin P and Marples B (1999) Adaptive response and induced resistance. CR Acad Sci III 322:167-75.         [ Links ]

Joksic G and Spasojevic-Tisma V (1998) Cromosome analysis of lymphocytes from radiatin workers in tritium-applying industry. Int Arch Occup Environ Health 71:213-220.         [ Links ]

Joksic G and Petrovic S (2004) Lack of adaptive response of human lymphocytes exposed in vivo to low doses of ionizing radiation. J Environ Pathol Toxicol Oncol 23:195-206.         [ Links ]

Joksic G, Pajovic SB, Stankovic M, Pejic S, Kasapovic J, Cuttone G, Calonghi N, Masotti L and Kanazir DT (2000) Chromosome aberrations, micronuclei, and activity of superoxide dismutases in human lymphocytes after irradiation in vitro. Cell Mol Life Sci 57:842-850.         [ Links ]

Jones SA, McArdle F, Jack CIA and Jackson MJ (1999) Effect of antioxidant supplement on the adaptive response of human skin fibroblasts to UV-induced oxidative stress. Redox Report 4:291-299.         [ Links ]

Jovtchev G and Stergios M (2003) Genotoxic and adaptive effect of cadmium chloride in Hordeum vulgare meristem cells. Compt Rend Acad Bulg Sci 56:75-80.         [ Links ]

Kleczkowska HA and Althaus FR (1996) The role of poly(ADP-ribosyl)altion in the adaptive response. Mutat Res 358:215-221.         [ Links ]

Ko M, Lao XY, Kapadia R, Elmore E and Redpath JL (2006) Neoplastic transformation in vitro by low doses of ionizing radiation: Role of adaptive response and bystander effects. Mutat Res 597:11-17.         [ Links ]

Lambin P, Fertil B, Malaise EP and Joiner MC (1994) Multiphasic survival curves for cells of human tumor cell lines: Induced repair or hypersensitive subpopulation? Radiat Res 138:32-36.         [ Links ]

Lanza V, Pretazzoli V, Olivieri G, Pascarella G, Panconesi A and Negri R (2005) Transcriptional response of human umbilical vein endothelial cells to low doses of ionizing radiation. J Radiat Res 46:265-276.         [ Links ]

Lazutka RJ and Mierauskiene J (2001) Cytogenetic damage of human lymphocytes treated with a phytopharmaceutical containing plant essential oils and madder root extract. Biologija 1:3-5.         [ Links ]

Lee HJ, Kang CM, Kim SR, Kim JC, Bae CS, Oh KS, Jo SK, Kim TH, Jang JS and Kim SH (2007) The micronucleus frequency in cytokinesis-blocked lymphocytes of cattle in the vicinity of a nuclear power plant. J Vet Sci 8:117-120.         [ Links ]

Leisinger U, Rufenacht K, Zehnder AJB and Eggen RIL (1999) Structure of a glutathione peroxidase homologous gene involved in the oxidative stress response in Chlamydomonas reinhardtii. Plant Sci 149:139-149.         [ Links ]

Leisinger U, Rufenacht K, Fischer B, Pesaro M, Spengler A, Zehnder AJB and Eggen RIL (2001) The glutathione peroxidase homologous gene from Chlamydomonas reinhardtii is transcriptionally up-regulated by singlet oxygen. Plant Mol Biol 46:395-408.         [ Links ]

Leonard BE (2007) Adaptive response: Part II. Further modeling for dose rate and time influences. Int J Radiat Biol 83:395-408.         [ Links ]

Lin CM and Mao IF (2004) Potential adverse health effects of low-level ionizing radiation exposure in a hospital setting. Arch Environ Health 59:342-347.         [ Links ]

Liu SZ (2003) On radiation hormesis expressed in the immune system. Crit Rev Toxicol 33:431-441.         [ Links ]

Maffei F, Angelini S, Forti GC, Lodi V, Violante FS, Mattioli S and Hrelia P (2002) Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: Influence of smoking status and other factors. Mutagenesis 17:405-409.         [ Links ]

Mahmood R, Vasudev V, Harish SK and Guruprasad KP (1996) Inducible protective processes in animal systems: Adaptive response to a low dose of methyl methanesulfonate in mouse bone marrow cells. Indian J Exp Biol 34:502-507.         [ Links ]

Marnett LJ, Riggins JN and West JD (2003) Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein. J Clin Invest 111:583-593.         [ Links ]

Marples B and Joiner M (1993) The response of Chinese hamster V79 cells to low radiation doses: Evidence of enhanced sensitivity of the whole cell population. Radiat Res 133:41-51.         [ Links ]

Marples B and Joiner M (2000) Modification of survival by DNA repair modifiers: A probable explanation for the phenomenon of increased radioresistance. Int J Radiat Biol 76:305-312.         [ Links ]

Marples B and Skov KA (1996) Small doses of high-linear energy transfer radiation increase the resistance of Chinese hamster V79 cells to subsequent X-irradiation. Radiat Res:382-387.         [ Links ]

Marples B, Wouters BG, Collis SJ, Chalmers AJ and Joiner MC (2004) Low-dose hyper-radiosensitivity: A consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells. Radiat Res 161:247-257.         [ Links ]

Matsumoto H, Takahashi A and Ohinishi T (2004) Radiation-induced adaptive response and bystander effects. Biol Sci Space 18:247-254.         [ Links ]

Mendez-Alvarez S, Leisinger U and Eggen RI (1999) Adaptive responses in Chlamydomonas reinhardtii. Int Microbiol 2:15-22.         [ Links ]

Miura Y (2004) Oxidative stress, radiation-adaptive responses, and aging. J Radiat Res 45:357-372.         [ Links ]

Mohammadi S, Taghavi-Dehaghani M, Gharaati MR, Masoomi R and Ghiassi-nejad M (2006) Adaptive response of blood lymphocytes of inhabitants residing in high background radiation areas of Ramsar- micronuclei, apoptosis and comet assays. J Radiat Res 47:279-285.         [ Links ]

Morales-Ramírez P and Mendiola-Cruz MT (2004) Kinetics of the early adaptive response to gamma rays: Induction of a cellular radioprotective mechanism in murine leukocytes in vivo. Biosci Rep 24:609-616.         [ Links ]

Mortazavi S, Cameron JR and Niroomand-rad A (2003a) Adaptive response studies may help choose astronauts for long-term space travel. Adv Space Res 31:1543-1551.         [ Links ]

Mortazavi SM, Cameron JR and Niroomand-rad A (2003b) Is the adaptive response an efficient protection against the detrimental effects of space radiation. Proceedings of the 28th International Cosmic Ray Conference, Tsukuba. Universal Academy Press Inc., Tokyo, pp 4299-4302.         [ Links ]

Mortazavi SMJ, Ikushima T and Mozdarani H (2003c) Variability of chromosomal radioadaptive response in human lymphocytes. Iran J Radiat Res 1:55-61.         [ Links ]

Neill SJ, Desikan R, Clarke A, Hurst RD and Hancock JT (2002) Hydrogen peroxide and nitric oxide as signalling molecules in plants. J Exp Bot 53:1237-1247.         [ Links ]

Nikolova T, Gateva S and Georgieva V (1999) Effects of heat shock and heavy metal salts pre-treatments on the frequency of TEM-induced chromatid aberrations in human peripheral blood lymphocytes in vitro. C Acad Bulg Sci 52:107-110.         [ Links ]

Olivieri G, Bodycote J and Wolff S (1984) Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 223:594-597.         [ Links ]

Osipov AN, Ryabchenko NI, Ivannik BP, Dzikovskaya LA, Ryabchenko VI and Kolomijtseva GYa (2003) A prior administration of heavy metals reduces thymus lymphocyte DNA lesions and lipid peroxidation in gamma-irradiated mice. J Phys IV France 107:987-992.         [ Links ]

Otsuka K, Koana T, Tauchi H and Sakai K (2006) Activation of antioxidative enzymes induced by low-dose-rate whole-body gamma irradiation: Adaptive response in terms of initial DNA damage. Radiat Res 166:474-478.         [ Links ]

Pajovic SB, Joksic G, Pejic S, Kasapovic J, Cuttone G and Masotti L (2001) Antioxidant dose response in human blood cells exposed to different types of irradiation. The Sciences 1:133-136.         [ Links ]

Panda KK, Patra J and Panda BB (1997) Persistence of cadmium-induced adaptive response to genotixicity of maleic hydrazide and methyl mercuric chloride in root meristem cells of Allium cepa L.: Differential inhibition by cycloheximide and buthionine sulfoximine. Mutat Res 389:129-139.         [ Links ]

Patra J, Sahoo MK and Panda BB (2003) Persistence and prevention of aluminium- and paraquat-induced adaptive response to methyl mercuric chloride in plant cells in vivo. Mutat Res 538:51-61.         [ Links ]

Pelevina II, Aleshchenko AV, Antoshchina MM, Gotlib VI, Kudriashova OV, Semenova LP and Serebrianyi AM (2003) The reaction of cell population to low level of irradiation. Radiats Biol Radioecol 43:161-166.         [ Links ]

Preston RJ (2005) Radiation biology: Concepts for radiation protection. Health Phys 88:545-556.         [ Links ]

Raaphorst GP, Malone S, Szanto J and Gray R (2000) Severe normal tissue complication correlates with increased in vitro fibroblast radiosensitivity in radical prostate radiotherapy: A case report. Int J Cancer 90:336-342.         [ Links ]

Raaphorst GP, Li LF and Yang DP (2006) Evaluation of adaptive responses to cisplatin in normal and mutant cell lines with mutations in recombination repair pathways. Anticancer Res 26:1183-1187.         [ Links ]

Rieger R and Michaelis A (1988) Heat shock protection against induction of chromatid aberrations is dependent on the time span between heat shock and clastogen treatment of Vicia faba root tip meristem cells. Mutat Res 209:141-144.         [ Links ]

Rieger R, Michaelis A, Jovtchev G and Nicolova T (1993) Copper sulphate and lead nitrate pretreatments trigger "adaptive responses" to the induction of chromatid aberrations by maleic hydrazide (MH) and /or JEM in Vicia faba, Hordeum vulgare, and human peripheral blood lymphocytes. Biol Zentralbl 112:18-27.         [ Links ]

Rigaud O and Moustacchi E (1996) Radioadaptation for gene mutation and the possible molecular mechanisms of the adaptive response. Mutat Res 358:127-134.         [ Links ]

Robson T, Joiner MC, Wilson GD, McCullough W, Price ME, Logan I, Jones H, McKeown SR and Hirst DG (1999) A novel human stress response-related gene with a potential role in induced radioresistance. Radiat Res 152:451-461.         [ Links ]

Robson T, Price ME, Moore ML, Joiner MC, McKelvey VJ, McKeown SR and Hirst DG (2000) Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: Implications for induced radioresistance. Int J Radiat Biol 76:617-623.         [ Links ]

Rohankhedkar MS, Mulrooney SB, Wedemeyer WJ and Hausinger RP (2006) The AidB component of the Escherichia coli adaptive response to alkylating agents is a flavin-containing, DNA-binding protein. J Bacteriol 188:223-230.         [ Links ]

Rubinelli P, Siripornadulsil S, Gao-Rubinelli F and Sayre RT (2002) Cadmium- and iron-stress-inducible gene expression in the green alga Chlamydomonas reinhardtii: Evidence for H43 protein function in iron assimilation. Planta 215:1-13.         [ Links ]

de Saint-Georges L (2004) Low-dose ionizing radiation exposure: Understanding the risk for cellular transformation. J Biol Regul Homeost Agents 18:96-100.         [ Links ]

Sakamoto-Hojo ET, Mello SS, Pereira E, Fachin AL, Cardoso RS, Junta CM, Sandrin-Garcia P, Donadi EA and Passos GAS (2003) Gene expression profiles in human cells submitted to genotoxic stress. Mutat Res 544:403-413.         [ Links ]

Salone B, Pretazzoli V, Bosi A and Olivieri G (1996) Interaction of low-dose irradiation with subsequent mutagenic treatment: Role of mitotic delay. Mutat Res 358:155-160.         [ Links ]

Santier S, Gilet R and Malaise E (1985) Induced radiation resistance during low-dose-rate gamma irradiation in plateau-phase Chlorella cells. Radiat Res 104:224-233.         [ Links ]

Sari-Minodier I, Orsière T, Bellon L, Pompili J, Sapin C and Botta A (2002) Cytogenetic monitoring of industrial radiographers using the micronucleus assay. Mutat Res 521:37-46.         [ Links ]

Sari-Minodier I, Orsière T, Auquier P, Martin F and Botta A (2007) Cytogenetic monitoring by use of the micronucleus assay among hospital workers exposed to low doses of ionizing radiation. Mutat Res 629:111-121.         [ Links ]

Sasiadek M, Schlade-Bartusiak K, Zych M, Noga L and Czemarmazowicz H (2002) Opposite responses in two DNA repair capacity tests in lymphocytes of head and neck cancer patients. J Appl Genet 43:525-534.         [ Links ]

Savina N, Dalivelya O and Kuzhir T (2003) Adaptive response to alkylating agents in the Drosophila sex-linked recessive lethal assay. Mutat Res 535:195-204.         [ Links ]

Sawant SG, Randers-Pehrson G, Metting NF and Hall EJ (2001) Adaptive response and the bystander effect induced by radiation in C3H 10T(1/2) cells in culture. Radiat Res 156:177-180.         [ Links ]

Schaffer M, Schwarz SB, Kulka U, Busch M and Dühmke E (2004) Adaptive doses of irradiation-an approach to a new therapy concept for bladder cancer? Radiat Environ Biophys 43:271-276.         [ Links ]

Schlade-Bartusiak K, Stembalska-Kozlowska A, Bernady M, Kudyba M and Sasiadek M (2002) Analysis of adaptive response to bleomycin and mitomycin C. Mutat Res 513:75-81.         [ Links ]

Scott BR (2004) A biological-based model that links genomic instability, bystander effects, and adaptive response. Mutat Res 568:129-143.         [ Links ]

Sedgwick B and Lindahl T (2002) Recent progress on the Ada response for inducible repair of DNA alkylation damage. Oncogene 21:8886-8894.         [ Links ]

Seo HR, Chung HY, Lee YJ, Bae S, Lee SJ and Lee YS (2006) p27Cip/Kip is involved in Hsp25 or inducible Hsp70 mediated adaptive response by low dose radiation. J Radiat Res 47:83-90.         [ Links ]

Shadley JD and Wolff S (1987) Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation. Mutagenesis 2:95-96.         [ Links ]

Shankar B, Pandey R and Sainis K (2006) Radiation-induced bystander effects and adaptive response in murine lymphocytes. Int J Radiat Biol 82:537-548.         [ Links ]

Skov K, Marples B, Matthews JB, Joiner MC and Zhou H (1994) A preliminary investigation into the extent of increased radioresistance or hyper-radiosensitivity in cells of hamster cell lines known to be deficient in DNA repair. Radiat Res 138:S126-129.         [ Links ]

Slapyte G, Jankauskiene A, Mierauskieneand J and Lazutka JR (2002) Cytogenetic analysis of peripheral blood lymphocytes of children treated with nitrofurantoin for recurrent urinary tract infection. Mutagenesis 17:31-35.         [ Links ]

Somers CM, Sharma R, Quinn JS and Boreham DR (2004) Gamma radiation-induced heritable mutations at repetitive DNA loci in out-bred mice. Mutat Res 568:69-78.         [ Links ]

Stoilov LM, Mullenders LH, Darroudi F and Natarajan AT (2007) Adaptive response to DNA and chromosomal damage induced by X-rays in human blood lymphocytes. Mutagenesis 22:117-122.         [ Links ]

Szumiel I (2005) Adaptive response: Stimulated DNA repair or decreased damage fixation? Int J Radiat Biol 81:233-241.         [ Links ]

Takahashi A, Ohinishi K, Yokota A, Kumagai T, Nakano T and Ohnishi T (2002) Mutation frequency of plasmid DNA and Escherichia coli following long-term space flight on Mir. J Radiat Res 43:S137-140.         [ Links ]

Takahashi A, Shibata N, Nishikawa S, Ohnishi K, Ishioka N and Ohnishi T (2006) UV-B light induces an adaptive response to UV-C exposure via photoreactivation activity in Euglena gracilis. Photochem Photobiol Sci 5:467-471.         [ Links ]

Tang HW, Liang HR, Zhuang ZX and He Y (2005) Low concentration of hydropuinone-induced adaptive response in hPARP-1 protein normal and deficient cells - Article in Chinese. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 23:274-277.         [ Links ]

Tiku AB and Kale RK (2001) Radiomodification of glyoxalase I in the liver and spleen of mice: Adaptive response and split-dose effect. Mol Cell Biochem 216:79-83.         [ Links ]

Tiku AB and Kale RK (2004) Adaptive response and split-dose effect of radiation on the survival of mice. J Biosci 29:111-117.         [ Links ]

Tosello ME, Biasoli MS, Luque AG, Magaró HM and Krapp AR (2007) Oxidative stress response involving induction of protective enzymes in Candida dubliniensis. Med Mycol 45:535-540.         [ Links ]

Tskhovrebova LB and Makedonov GP (2004) On the mechanism of adaptive response in human cells - Article in Russian. Radiats Biol Radioecol 44:657-661.         [ Links ]

Ulsh BA, Miller SM, Mallory FF, Mitchel REJ, Morrison DP and Boreham DR (2004) Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation. J Environ Radioact 74:73-81.         [ Links ]

Upton AC (2001) Radiation hormesis: Data and interpretations. Crit Rev Toxicol 31:681-695.         [ Links ]

Vaganay-Juery S, Muller C, Marangoni E, Abdulkarim B, Deutsch E, Lambin P, Calsou P, Eschwege F, Salles B, Joiner M, et al. (2000) Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to low-dose irradiation. Br J Cancer 83:514-518.         [ Links ]

Venkat S, Apte SK, Chaubey RC and Chauhan PS (2001) Radioadaptive response in human lymphocytes in vitro. J Environ Pathol Toxicol Oncol 20:165-175.         [ Links ]

Verschooten L, Declercq L and Garmyn M (2006) Adaptive response of the skin to UVB damage: Role of the p53 protein. Int J Cosmetic Sci 28:1-7.         [ Links ]

Vranová E, Inzé D and Van Breusegem F (2002) Signal transduction during oxidative stress. J Exp Bot 53:1227-1236.         [ Links ]

Wang GJ and Cai L (2000) Induction of cell proliferation hormesis and cell-survival adaptive response in mouse hematopoietic cells by whole-body low-dose radiation. Toxicol Sci 53:369-376.         [ Links ]

Wang X, Samet JM and Ghio AJ (2006) Asbestos-induced activation of cell signaling pathways in human bronchial epithelial cells. Exp Lung Res 32:229-243.         [ Links ]

Wojewózka M, Kruszewski M and Szumiel I (1996) Anti-CD38 prevents the development of the adaptive response induced by X-rays in human lymphocytes. Mutagenesis 11:593-596.         [ Links ]

Wolff S (1996) Aspects of the Adaptive response to very low doses of radiation and other agents. Mutat Res 358:135-142.         [ Links ]

Wolff S (1998) The adaptive response in radiobiology: Evolving insights and implications. Environ Health Persp 106:S277-283.         [ Links ]

Wolff S, Afzal V, Wiencke JK, Olivieri G and Michaeli A (1988) Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA. Int J Radiat Biol 53:39-47.         [ Links ]

Yan G, Hua Z, Du G and Chen J (2006) Adaptive response of Bacillus sp. F26 to hydrogen peroxide and menadione. Curr Microbiol 52:238-242.         [ Links ]

Zakeri F and Assaei RG (2004) Cytogenetic monitoring of personnel working in angiocardiography laboratories in Iran hospitals. Mutat Res 562:1-9.         [ Links ]

Zasukhina GD, Vasyleva IM and Semyachkina AN (2000) Independence of DNA repair after gamma irradiation and radioadaptive response in lymphocytes of patients with Bloom syndrome - In Russian. Radiats Biol Radioecol 40:513-515.         [ Links ]

Zhou H, Randers-Pehrson G, Waldren CA and Hei TK (2004) Radiation-induced bystander effect and adaptive response in mammalian cells. Adv Space Res 34:1368-1372.         [ Links ]

 

 

Send correspondence to:
Stephka G. Chankova
Department of Bioindication and Environmental Risk, Central Laboratory of General Ecology, Bulgarian Academy of Sciences
2 Gagarin Str., 1113 Sofia, Bulgaria
E-mail: stephchbg@yahoo.co.uk

Received: October 10, 2007; Accepted: December 21, 2007.

 

 

Associate Editor: Carlos F.M. Menck

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