Atrazine, which has been used worldwide as a pesticide, is now known to exert endocrine disrupting (antiandrogenic) effects in mammals. In this study, modifying effects of dietary feeding of 500 and 1000 p.p.m. atrazine on the development of androgen-dependent prostate cancer were investigated using male probasin/SV40 T antigen transgenic (TG) rats. As administration of atrazine has now been identified as causing a decrease in bodyweight, a dietary-restricted TG rat group was also included in order to elucidate the influence of reduction of calorie intake per se on the development of prostate cancer. At week 13, almost the entire lobes of the prostate were occupied with tumor lesions, with no clear intergroup differences in the incidences and multiplicities. Therefore, morphometrical assessment ratios of the prostate epithelial area to the whole prostate tissue area were evaluated. The ratio in the lateral lobe of the 1 000 p.p.m. atrazine-treated group was significantly decreased, and there was a tendency to decrease in the ratios in the dorsal lobe of the atrazine-treated groups. However, dietary restriction itself without atrazine treatment caused the same reduction to a similar or greater extent. Testosterone levels were not affected by atrazine administration or dietary restriction. Our results indicate that the observed atrazine-related suppression of prostate carcinogenesis was probably caused by the decrease in calorie intake, rather than by atrazinerelated endocrine disruption. (Cancer Sci 2005; 96: 221-226)
To evaluate the impact of p27 on carcinogenesis in various organs, N-methyl-N-nitrosourea (MNU), a direct-acting alkylating agent, was given to p27 knock-out mice. Groups of 20-40 male and female mice with null, hetero- or wild-type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27-null males as compared with both wild- and hetero-type animals. Moreover, in both p27(+/+) and p27(+/-) cases, the rates for p27-positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27-positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU-induced carcinogenesis.
Gap junctions, composed from molecules called connexins, play important roles in cell-to-cell communication and aberrant gap junctional intercellular communication (GJIC) has been reported in many types of cancers. We have established transgenic rats bearing a dominant negative mutant of the connexin 32 gene under control of the albumin promoter. In these rats, GJIC is markedly decreased in the liver, and is associated with increased induction of preneoplastic foci after a single treatment of diethylnitrosamine. In the present study, in order to explore whether organs other than the liver would demonstrate increased susceptibility to a carcinogen, we treated these transgenic rats (having disrupted GJIC of the liver) with diisopropanolnitrosamine (DHPN), a carcinogen targeting multiple organs, such as the liver, lung, kidney and thyroid gland. We found that increased susceptibility for the carcinogenicity was evident only in the liver, but not in the lung, kidney and thyroid gland. This result indicates that disrupted GJIC in the liver influences the liver carcinogenesis, but has no effect on carcinogenesis in other organs. (J Toxicol Pathol 2006; 19: 93-97)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.