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 systemi c intraperitoneal (i.p.) administration method for the induction of ma mmary carcinomas in female Sprague-Dawley (S-D) rats. The effectivenes s was also tested in genetically resistant female Copenhagen (Cop) rat s. The 10 mg crystalline MNU was dusted directly onto the right-inguin al 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 wee kly and killed when the tumor reached 1-2 cm in diameter or were necro psied 30 weeks after carcinogen treatment. In S-D rats, all of the 78 tumors produced by dusting were adenocarcinomas. By contrast, 40 tumor s produced i.p. were adenocarcinomas, 1 was fibroadenoma, and 5 were l actating adenomas. The cumulative incidence of mammary carcinoma was h igh in the dusting and the i.p. groups (12/12; 100% and 11/13; 84%, re spectively). However, the dusting groups showed a high number of carci noma per rats (6.5 vs. 3.6; P < 0.01) and short cancer latency (13.8 w eeks v.s. 28.1 weeks; P < 0.001) than the i.p. groups. In Cop rats, al though low (4/11; 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-admi nistration, the direct dusting technique is an effective method and of fers added advantages of ease for the induction of mammary carcinomas in rats.