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 > or =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.
Sato
Mutsuya
M
Department of Pathology II, Kansai Medical University, Moriguchi, 570-8506 Osaka, Japan.
Pei
Ren Jeng
RJ
Yuri
Takashi
T
Danbara
Naoyuki
N
Nakane
Yasushi
Y
Tsubura
Airo
A
D000367:Age Factors; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D007529:Isoflavones / Q000633:toxicity*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D008770:Methylnitrosourea / Q000633:toxicity; D048789:Phytoestrogens; D028321:Plant Preparations / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000633:toxicity*
D000477:Alkylating Agents; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D013267:Stilbenes; D008770:Methylnitrosourea; D000077185:Resveratrol