Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide.

Unidades de conservação da natureza sofrem historicamente de problemas envolvendo, por exemplo, administração pública e legitimação popular, o que reflete quadros de ineficiência e conflitos locais em vários níveis. Nesse contexto, a Área de Proteção Ambiental de Petrópolis é abordada no presente trabalho, com o objetivo de se traçar um panorama sistêmico de tal proposta de sustentabilidade, observando a história local, a gestão pública e a participação popular. É proposta, portanto, uma análise da paisagem local de maneira sistêmica e integrada, sob um referencial teórico que engloba: políticas locais, manejo de unidades de conservação, conflitos ambientais e participação social. Como resultados, pode-se destacar um quadro de gestão pública de baixa eficiência e conflitos de interesse e gestão. O caráter unilateral das tomadas de decisão e confecção do zoneamento ambiental, aliadas ao contexto de ineficiência histórica da gestão dos órgãos públicos competentes foram identificados como entraves ao bom funcionamento da unidade. Criada em 1982, a proposta da APA se apresenta ainda hoje aberta e inovadora; porém, tal inovação no modelo de unidades de conservação esbarra na gestão pública de baixa eficiência e na visão preservacionista dominante nas esferas técnicas. Destaca-se, ainda: o conflito entre as diferentes esferas do poder público, e os conflitos entre os poderes locais e os interesses em conservação da natureza como fenômenos que dificultam a consecução de propostas práticas de conservação. Defende-se que a observação da diversidade dos atores existentes na paisagem da APA e a participação social efetiva sejam caminhos para se atingir os objetivos de sustentabilidade, e o uso do conceito de redes sociotécnicas será de grande valia para as novas abordagens que se propõem. O segmento universitário é indicado como provedor de importantes elos sociotécnicos que servirão como alavancas à participação social solidária, e assim ao conhecimento e aproximação aos atores e problemas locais.

Nature conservation units have historically suffered with problems involving, for example, public administration and popular legitimacy, which reflect in inefficiency boards and local conflicts at various levels. On this context, the Environmental Protection Area of Petrópolis (APA Petrópolis) is investigated on this contribution, following the intention to give a systemic overview of this sustainability proposal, observing the local history, public management and popular participation. We propose, indeed, an systemic and integrated analisys of the local landscape, involving studies in local: politics, conservation units management, environmental conflicts. As results, we describe low eficiency public administration anda conflicts of interest and management. The unilateral character of decision making and the environmental zoning, combined with the historical context of inefficient management of responsible public agencies were identified as obstacles to the well functioning of the unit. Created in 1982, the APA proposal is still presented as open and innovative; nevertheless, the innovation suggested by this model collides to the low efficiency of public administration and the preservationist vision, dominant at the technical spheres. It is noteworthy, in addiction: the conflict between the different governmental spheres, as well the conflicts between local interests and the nature conservation act as phenomena that complicate the achievement of proposed conservation practices. We defend that the observation on the diversity of actors playing a role in the APA landscape, and the effective social participation are ways to achieve sustainability goals, and the use of the concept of sociotechnical nets would be valuable to the new views proposed. The university segment is indicated as a provider of important socio-technical links that will serve as levers for social participation, and thus to the knowledge and approach to local actors and local problems.

Nitrocompostos, como N-nitrosodietilamina (NDEA), podem ser formados pela reação entre uma amina secundária e agentes nitrosantes e são suspeitos de estarem envolvidos na formação de tumores em humanos. NDEA é considerada um carcinógeno fraco e ensaios genotóxicos provavelente pela utilização de um sistema de ativação ineficiente e/ou pela utilização de um eficiente sistema de reparo. Neste trabalho, nós avaliamos a sensibilidade de ensaios com Alliu cepa L. e Tradescantia pallida var. purpurea (Trad-SH) à genotoxicidade e mutagenicidade induzidas por diferentes concentrações de NDEA (0,1; 0,5; 5 e 25mM) por 3h, por 3 dias consecutivos, incluindo controle negativo (água destilada) e controle positivo, hidrazida maleica (MH 30mg/mL). Depois do tratamento, as raízes foram hidrolizadas, esmagadas e o índice mitótico (IM) e anormalidades citológicas foram contadas. Os resultados revelaram um efeito citostático de NDEA (0,5 e 5mM), pela significante redução do IM. Chromosome stickiness sugere um efeito citotóxico de NDEA. T pallida purpurea não respondeu ao mutágeno com um padrão dose dependente. Em conclusão, nossos estudos indicaram que raízes de Allium cepa L. possue sensibilidade na detecção genotóxica de NDEA, mas não para o ensaio Trad-SH.

N-nitroso compounds, such as N-nitrosodiethylamine (NDEA), can be formed by the reaction of secundary amines with nitrosating agents, and are suspected to be involved in tumors in humans. NDEA has been considered a weak carcinogen in genotoxic assays probably due to the inefficient nitrosamine activation system that is used and/or to the efficient repair system. In this work, we evaluated the sensibility of Allium cepa L. root tips and Tradescantia stamen hair mutation assay (Trad-SH) using Tradescantia pallida var. purpurea for NDEA (0.1; 0.5; 5 and 25mM) genotoxicity and mutagenicity induction. Allium cepa L. was treated with different NDEA concentrations for 3h, for 3 consecutive days, including negative control (distilled water) and positive control maleic hydrazide (MH 30mg/mL). After treatment, the roots were hydrolyzed, squashed, and the mitotic index (MI) and cytological abnormalities were scored. The results revealed a cytostatic effect of NDEA (0.5 and 5mM), showing a significant reduction in the MI. Chromosome stickiness suggests a NDEA toxic effect. T. pallida purpurea did not respond to mutagens with a dose-dependent pattern. In conclusion, our study indicates that the root tips of Allium cepa L. have sensibility to detect NDEA genotoxicity, but not for Trad-SH test.

Hydrogen peroxide is an important reactive oxygen species (ROS) that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER), nucleotide excision repair (NER) and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm) and H2O2, the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H2O2 under low-iron conditions.