Carcinogenesis and aging. I. Modifying effects of aging on N-methyl-N-nitrosourea-induced carcinogenesis in female rats.

3- or 14-month-old female rats were intravenously injected N-nitroso-N-methylurea (MNU), 50 mg/kg body weight, 2 or 4 times weekly. There was a direct correlation between the incidence of mammary carcinomas and MNU doses. Kidney tumors occurred inversely proportional to the dose of the carcinogen. Mammary adenocarcinomas were only observed in young MNU-treated rats. Cervicovaginal malignant tumors were only observed in old MNU-treated rats. The incidence of hematopoietic system tumors was the same in animals of both age groups. Rats treated with MNU showed acceleration of benign spontaneous tumor development. The effect of aging on the initial stage of MNU-induced carcinogenesis is believed to be determined by age-associated changes in the proliferative activity of target tissues. The effect of aging on the further development of carcinogenesis may be caused by age-associated hormonal, metabolic, and immunological shifts.