O marolo (Annona crassiflora Mart.) é uma fruta do cerrado brasileiro e fonte de compostos fitoquímicos com grande variedade de atividades biológicas, incluindo eliminação de radicais livres. Entretanto, em estudos anteriores, essa fruta nativa mostrou-se como potencializadora do processo mutagênico in vivo. Objetivou-se, neste estudo, investigar os efeitos da ingestão da polpa de marolo sobre a proliferação de células do cólon e no desenvolvimento de lesões pré-neoplásicas por meio de focos de criptas aberrantes (ACF) em ratos Wistar. Os animais foram alimentados com dieta comercial ou suplementada com polpa de marolo nas proporções de 1%, 10% ou 20% (m/m), durante 4 semanas, ou 20 semanas. Como agente indutor da carcinogênese de cólon foi utilizado o dicloridrato de 1,2-dimetilhidrazina (4 doses, 40 mg kg-1 cada). Após a eutanásia, as amostras de sangue, fígado e cólon foram coletadas para determinações bioquímicas, estresse oxidativo ou análise de desenvolvimento de Focos de Criptas Aberrantes (FCA), respectivamente. A análise imunohistoquímica da mucosa do cólon foi realizada, utilizando anticorpos contra o antígeno nuclear de proliferação celular (PCNA) e β-catenina em FCA. Não houve desenvolvimento de FCA no cólon nos grupos tratados exclusivamente com polpa de marolo. Além disso, a análise de estresse oxidativo e bioquímico, PCNA e de desenvolvimento (multiplicidade, número ou localização celular da β-catenina) permaneceram inalteradas como resultado da ingestão da polpa de marolo. Assim, os resultados sugerem que a ingestão do fruto não exerceu efeito protetor contra a carcinogênese induzida pela DMH e, principalmente, não apresentou efeitos mutagênicos ou carcinogênicos pelos métodos avaliados.

A. crassiflora Mart. a Brazilian savannah fruit, is a source of phytochemical compounds that possess a wide array of biological activities, including free radical scavenging. This native fruit proved to potentialize the mutagenic process in previous in vivo investigations. The aim of the present study was to investigate the effects of A. crassiflora Mart. pulp intake on colonic cell proliferation and on the development of Aberrant Crypt Foci (ACF) in male Wistar rats. The animals were fed with either a commercial diet or a diet supplemented with A. crassiflora Mart. pulp mixed in 1%, 10% or 20% (w/w) for 4 weeks or 20 weeks. The carcinogen 1,2-dimethylhydrazine dihydrochloride (4 doses, 40 mg kg-1 each) was used to induce colonic ACF. After euthanasia, the blood, liver and colon samples were collected for biochemical determinations, oxidative stress or ACF development analysis, respectively. Immunohistochemical analyses of the colonic mucosa were performed using antibodies against proliferating cell nuclear antigen (PCNA) in normal-appearing colonic crypt and β-catenin in ACF. There was no ACF development in the colon from groups treated with A. crassiflora Mart. pulp. Also, the biochemical and oxidative stress analysis, PCNA labeling and ACF development (number, multiplicity or cellular localization of β-catenin) were unchanged as a result of marolo pulp intake. Thus, the present results suggest that A. crassiflora Mart. pulp intake did not exert any protective effect in the colon carcinogenesis induced by DMH in rats.

The aim of this work was to analyze the cell proliferation and apoptosis indexes on the 18th and 21st days of pregnancy of diabetic rats and to correlate with maternal glycemia and perinatal outcomes. Placentas from 20 Wistar rats were collected and divided into four experimental groups: control and diabetic of 18 and 21 days of pregnancy. The cell proliferation was analyzed using the PCNA expression and apoptosis by the TUNEL method. It was observed that PCNA and TUNEL indexes decreased from day 18 to 21 of pregnancy in the placentas of diabetic rats and these values were lower than control groups. Diabetic dams presented higher percentage of small for pregnancy age (SPA) fetuses. However, there was no difference between the PCNA and TUNEL indexes in SPA and N-SPA fetuses in all the groups and these indexes were not correlated to maternal glycemic. Thus, placental cell proliferation and apoptosis did not interfere in the intrauterine growth restriction.

Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4- liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group.