Influence of atrazine administration and reduction of calorie intake on prostate carcinogenesis in probasin/SV40 T antigen transgenic rats

Abstract

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)

Characterization of SV-40 Tag rats as a model to study prostate cancer

“…Therefore, the estrogen to androgen ratio was not correlated with prostate cancer development in the SV-40 Tag rats compared to non-transgenic rats. Testosterone concentrations (free and conjugated testosterone) in the blood serum were consistent with previously reported levels in SV-40 Tag rats [28-30], whereas DHT and estradiol concentrations in SV-40 Tag rats have yet to be published. Moreover, testosterone and DHT concentrations, as well as DHT to testosterone ratios in the blood serum of Sprague Dawley non-transgenic rats, were within range of previously reported values [31-33].…”

Atrazine promotes RM1 prostate cancer cell proliferation by activating STAT3 signaling

“…Atrazine (99% purity), SDS, TEMED, Acrylamide, N, N-Dimethyl-bis-acrylamide, DTT and PMSF were obtained from Sigma Chemical Co. (USA). ATR stock solutions (10 -2 mol/l) were prepared in corn oil (13), and kept at 4˚C for a maximum of 1 week. Anti-Grim-19, Stat3, MMP9, MMP2, VEGF, PCNA, P53, c-myc, Cyclin B1, Cyclin D1, Bcl-2, Bax, and Caspase-3 primary antibodies, as well as secondary antibodies were acquired from Proteintech Group (USA).…”

Body Mass Index, Weight Change, and Risk of Prostate Cancer in the Cancer Prevention Study II Nutrition Cohort

“…In our study, the risk of being diagnosed with prostate cancer was decreased among men who experienced weight loss in the 10 years preceding enrollment, although the association was only statistically significant for men diagnosed with nonmetastatic high-grade prostate cancer, supporting a role for caloric restriction on prostate cancer carcinogenesis. Caloric restriction decreases cellular proliferation (61), enhances apoptosis (62), and delays prostate cancer development in genetically susceptible mice (63,64). In addition, caloric restriction reduces tumor growth, lowers circulating levels of IGF-I, and decreases the expression of vascular endothelial growth factor in a human prostate cancer -transplanted mice model (65).…”