Cytogenetic damage and tumor incidence in mouse skin after single, topical applications of 7,12-dimethylbenz[a]anthracene

Abstract

Micronucleus induction, chromosomal damage and aneuploidy were evaluated in whole skin keratinocyte cultures derived from HRA/Skh mice after single in vivo applications of 0.256, 2.56 and 25.6 μg (1, 10 and 100 nmoles) of the carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). These genotoxicity end-points were compared with papilloma and carcinoma occurrence at the same dose levels of carcinogen. While the lower 2 doses of DMBA significantly increased the incidence of micronuclei and other chromosomal anomalies in keratinocytes, the two highest doses resulted in a significantly increased papilloma yield (0.297 and 3.895 papillomas/mouse) and incidence (24.3 and 100%). Carcinomas appeared only at the highest dose (0.125 carcinomas/mouse; 5% incidence). Neither papillomas nor carcinomas occurred in solvent-treated control mice. None of the three applied doses induced aneuploidy under conditions leading to an increase in tumors and/or chromosomal damage. © 1993.