Effects of Prepubertal Indole-3-Carbinol Treatment on Development of N-Methyl-N-Nitrosourea-induced Mammary Carcinomas in Female Sprague-Dawley Rats

Abstract

Background: Indole-3-carbinol (I3C), which is present in cruciferous vegetables, has been shown to prevent the development of mammary cancer when administered to adult animals. However, no studies have been reported on the effects of prepubertal short-term I3C treatment on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis. Materials and Methods: Prepubertal female Sprague-Dawley rats were administered the vehicle (Group 1) or I3C (Group 2, 250 mg/kg/day at 15 and 16 days of age; Group 3, 50 mg/kg/day at 15 and 16 days of age; Group 4, 50 mg/kg/day at 15, 16, 29 and 30 days of age; Group 5, 50 mg/kg/day at 29 and 30 days of age). All rats were administered 50 mg/kg MNU at 22 days of age. Rats were sacrificed at 34 weeks of age or when their largest mammary tumor reached a diameter of ≥1 cm. Body weight gain, vaginal opening, estrous cyclicity and mammary carcinogenesis were compared between the groups. Results: Rats administered 250 mg/kg I3C exhibited acute toxicity, and 40% of that group died soon after administration of I3C. There was no significant difference in body weight and relative uterine-ovarian weight of surviving rats between groups at the end of the experiment. However, rats from Group 2 and Group 3 exhibited earlier vaginal opening and prolonged estrous cyclicity, respectively. I3C treatment before and after MNU administration (Group 4) tended to reduce mammary carcinoma incidence (percentage of mammary carcinomas with a diameter of ≥1 cm) and multiplicity (number of all-sized mammary carcinomas per rat), and prolonged the latency (time from MNU administration to point when mammary tumors grew to a diameter of ≥1 cm) compared with the vehicle (control) group. Mammary carcinogenesis was not altered by other I3C treatments. Conclusion: Prepubertal I3C treatment before and after carcinogen exposure appeared to provide an insignificant protection against MNU-induced mammary carcinogenesis.