Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea

Abstract

While most data in the literature indicate that chemically-induced mammary carcinogenesis in the rat proceeds through morphologically identifiable stages, little quantitative data exist on the frequency of their occurrence. A carcinogen induction protocol is reported that defines conditions under which approximately 38% of detectable lesions in the abdominal-inguinal mammary glands were histologically classified as either intraductal proliferations or ductal carcinoma in situ. The remainder of the lesions were classified as carcinomas. This response was observed in a group of 30 female Sprague-Dawley rats injected i.p. with 50 mg 1-methyl-1-nitrosourea (MNU)/kg body wt at 21 days of age. The experiment was terminated 35 days following carcinogen administration. The methods used to prepare whole mounts and to identify, excise and process lesions in the whole mounts to permit histological classification are described in detail. This carcinogenesis protocol also induced a significant palpable tumor response. The first palpable tumor, histologically classified as an adenocarcinoma, was observed 30 days post carcinogen administration. When the experiment was terminated (35 days post MNU), the cumulative incidence of palpable carcinomas was 60%. The rapidity of the carcinogenic response was remarkable. Unlike the i.v. administration of 7,12-dimethylbenz[a]anthracene (DMBA) to rats of this age, MNU injection resulted in > 99% incidence of palpable mammary gland tumors that were malignant. The data reported in this paper confirm and support the pathogenetic pathway described for the induction of mammary tumors in the rat by DMBA. The induction of mammary carcinogenesis in immature animals described in this paper may be of value in the investigation of early morphologically identifiable stages of this disease process as well as providing an extremely rapid method for tumor induction.