Cell proliferation and prevalence of ras gene mutations in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors.

Exposure of female inbred Sprague-Dawley Curl rats to intragastric 7,12-dimethylbenz(a)anthracene (DMBA) resulted in a variety of benign and malignant mammary tumors exhibiting a wide spectrum of proliferative activity as measured by [3H]-thymidine autoradiography. On the basis of earlier observations of 21% H-ras codon 61 mutations in DMBA-induced rat mammary tumors reported by Zarbl et al., the prevalence of this type of ras gene mutation was studied in relation to the rate of proliferation in individual benign and malignant tumors. In a series of 50 mammary tumors exhibiting highly different proliferation activities we did not detect any H-ras codon 61 mutations after allele-specific dot blot hybridization of PCR-amplified material obtained from paraffin sections. Neither mode of proliferation nor type of differentiation appears related to H-ras codon 61 mutations. The relevance of activated ras genes for rat mammary carcinogenesis appears restricted to model systems using N-methyl-N-nitro-sourea (MNU) as initiating carcinogen.