Mammary carcinogenesis in rats in relation to age at time of N-nitroso-N-methylurea administration

The effects on mammary carcinogenesis when N-nitroso-N-methylurea (NMU) is administered to rats of different ages were studied. Female outbred Sprague-Dawley rats received two iv injections of NMU (5 mg/100 g body wt/injection) 1 week apart beginning at either 35, 50, 80, 140, or 200 days of age. Animals were killed 6 months after the initial NMU injection, and all mammary tumors were histologically classified. The percent incidence of mammary carcinomas for each age group was as follows: 100%, 35 days old; 94%, 80 days old; 59%, 80 days old; 30%, 140 days old; and 22%, 200 days old. Rats receiving NMU at a young age also exhibited a greater number of carcinomas per rat with latent periods that were in general shorter than those of rats treated at later ages. Since NMU does not require metabolic activation, the observed decrease in chemically induced mammary tumors in aging rats appears to be primarily due to changes occurring within the mammary gland.