Induction of mammary carcinomas by the direct application of crystalline N-methyl-N-nitrosourea onto rat mammary gland

The effectiveness of the direct application of crystalline N-methyl-N-nitrosourea (MNU) onto the mammary gland was compared with the systemic intraperitoneal (i.p.) administration method for the induction of mammary carcinomas in female Sprague-Dawley (S-D) rats. The effectiveness was also tested in genetically resistant female Copenhagen (Cop) rats. The 10 mg crystalline MNU was dusted directly onto the right-inguinal mammary gland, or 50 mg/kg body weight MNU solution was given i.p. at 50 days of age. Animals were palpated for tumor detection twice weekly and killed when the tumor reached 1–2 cm in diameter or were necropsied 30 weeks after carcinogen treatment. In S-D rats, all of the 78 tumors produced by dusting were adenocarcinomas. By contrast, 40 tumors produced i.p. were adenocarcinomas, 1 was fibroadenoma, and 5 were lactating adenomas. The cumulative incidence of mammary carcinoma was high in the dusting and the i.p. groups (1212; 100% and 1113; 84%, respectively). However, the dusting groups showed a high number of carcinoma per rats (6.5 vs. 3.6; P < 0.01) and short cancer latency (13.8 weeks v.s. 28.1 weeks; P < 0.001) than the i.p. groups. In Cop rats, although low (411; 36%), adenocarcinomas were developed by the dusting method. In both strains, adenocarcinomas displayed various degrees of differentiation but no evidence was found for metastasis. For MNU-administration, the direct dusting technique is an effective method and offers added advantages of ease for the induction of mammary carcinomas in rats.