Prepubertal resveratrol exposure accelerates N-methyl-N-nitrosourea-induced mammary carcinoma in female Sprague-Dawley rats

The major object of this study was to characterize the effect of prepubertal trans-3,4',5-trihydroxystilbene (resveratrol) exposure on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Prepubertal rats ( 15 to 19 days of age) were treated daily with either 10 or 100 mg/kg resveratrol for 5 days, and were compared with resveratrol-untreated animals (30 rats in each group). Six rats in each group were autopsied at 49 days of age, and their growth was evaluated. All remaining rats were given 50 mg/kg MNU, followed by monitoring for occurrence of mammary carcinoma. A dose of 100 mg/kg (but not 10 mg/kg) resveratrol significantly increased incidence of rat with mammary carcinomas greater than or equal to 1 cm and multiplicity (all histologically detected mammary carcinomas per rat), but did not affect latency, compared with untreated controls. Resveratrol did not affect body weight increase, but 100 mg/kg resveratrol caused slightly earlier vaginal opening. Although all rats cycled, resveratrol-treated animals exhibited significantly increased irregularity of estrous cycle, spending more time in the estrus phase. Thus, short resveratrol treatment of prepubertal female rats affected endocrine function, and accelerated development of MNU-induced mammary carcinomas. (C) 2003 Elsevier Ireland Ltd. All rights reserved.