Effects of DMBA Preparation on DMBA-Induced Rat Mammary Carcinogenesis

Abstract

We compared two protocols for 7,12-dimethylbenz[ a ]anthracene (DMBA)-induced mammary carcinogenesis. DMBA (20 mg/ml) was prepared at room temperature or at 60°C and administered by gavage to 50-day-old Sprague-Dawley rats. Two days post-DMBA, mammary epithelial DNA was 32 P-postlabeled. At 12 weeks post-DMBA, tumor DNA was screened for H- ras codon 61 mutations using an enriched polymerase chain reaction (EPCR). The number of in situ carcinomas (3.0 - 2.7 vs. 2.5 - 2.7), invasive carcinomas (1.1 - 1.6 vs. 0.6 - 0.8), and H- ras codon 61 mutations (34 - 13% vs. 23 - 13%) were statistically not different ( p = 0.05) between the groups. The relative adduct levels in mammary organoids were significantly ( p h 0.001) greater in the 60°C (568 - 158) than the room temperature (150 - 130) group. While DMBA-DNA adduct levels differed significantly between these protocols, this did not correlate with significant differences in tumor pathologies or H- ras codon 61 mutations.