Effects of sex and age on DMBA:DNA binding in epidermis of SENCAR mice following topical administration of dimethylbenz[ a]anthracene

Abstract

Epidermal DMBA:DNA adduct formation was determined in male and female SENCAR mice following short-term exposure to 7,12-dimethylbenz[ a]anthracene (DMBA). While qualitatively the adduct profiles are similar in both male and female mice, male mice generally had higher levels of each individual adduct as well as a greater total binding of DMBA to DNA at 6 and 48 h after topical administration. Additionally, the effect of age on total DMBA:DNA binding was examined in epidermis of male mice. While there appeared to be some effect of age on total DMBA:DNA binding at 6 h after administration, these differences were not statistically significant. However, DMBA:DNA binding at 48 h was found to vary significantly with age. The levels of binding were greatest between 40 and 54 days of age. These studies demonstrate the importance of considering both the age and sex of animals when examining the metabolism and binding of DMBA and in muscle skin tumor induction experiments using DMBA as an initiator.