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In a previous study, we established a 2-stage uterine carcinogenesis model that is useful for detecting modifying effects of endocrine disrupting chemicals (EDCs) featuring administration of N-ethyl-N-nitrosourea (ENU) as an initiator to female heterozygous p53 deficient CBA mice [p53 (+/-) mice]. In addition, we demonstrated that ethinylestradiol with strong estrogenic activity, but not methoxychlor with weak estrogenic activity, showed promoting effects on uterine carcinogenesis. In the present study, to clarify the effects of other EDCs with weak estrogenic activity on development of uterine tumors, female p53 (+/-) CBA mice received an intraperitoneal injection of 120 mg/kg body weight of ENU followed by the diet containing 1% bisphenol A (BpA), 20% roasted-ground soybean (Kinako) (SB) or no further treatment for 26 weeks. Animals of the ENU+BpA and ENU+SB groups showed no significant differences in body weight gain compared to the ENU alone group. Lower values in absolute and relative uterine weights were observed in the ENU+BpA and ENU+SB groups compared to the ENU alone group, but no significant differences were observed in the incidence of uterine endometrial stromal sarcomas and their PCNA labeling indices among the groups. The results in the present study indicate that 1% BpA and 20% SB in diet have no modifying effects on uterine carcinogenesis in p53 (+/-) CBA mice initiated with ENU.

journal of toxicologic pathology

Lack of Modifying Effects of Bisphenol A and Roasted-Ground Soybean (Kinako) on N-ethyl-N-nitrosourea-Induced Uterine Carcinogenesis in Heterozygous p53 Deficient CBA Mice.