Promoting Effects of Ethinylestradiol but not Atrazine on <i>N</i>-ethyl-<i>N</i>-nitrosourea-induced Uterine Carcinogenesis in ICR Mice

Abstract

In order to assess the modifying effects of atrazine (ATR) on uterine endometrial carcinogenesis, female ICR mice received an intra-uterine injection via the vagina of 50 mg/kg body weight of N-ethyl-N-nitrosourea (ENU), followed by no further treatment, by a diet containing 5, 50 or 500 ppm ATR or by a diet containing 2.5 ppm ethinylestradiol (EE) for 26 weeks. In the ENU + EE (positive control) group, depression of body weight gain was seen throughout the treatment period, and the incidence of uterine endometrial proliferative lesions such as adenocarcinomas and atypical hyperplasias, and PCNA positive indices were significantly increased as compared to the ENU alone group. On the other hand, although only slight depression of body weight was seen throughout the study in the ENU + 500 ppm ATR group, but no significant differences in uterine weights, incidence of uterine proliferative lesions with their PCNA positive indices and the immunohistochemical expression of ERα were found in all of the ENU + ATR groups as compared with those of the ENU alone group. The results in the present study indicate that ATR up to 500 ppm in diet has no modifying effects on uterine carcinogenesis in ICR mice initiated with ENU.