Response differences among mouse strains in DNA damage and skin carcinogenicity of 7,12-dimethylbenz[a]anthracene are due to inducible aryl hydrocarbon hydroxylase activity.

Abstract

Strain differences of mice in the induction of DNA damage in peripheral blood cells and skin tumors were investigated using 7,12-dimethylbenz[a]anthracene (DMBA). DMBA-induced DNA damage and skin tumorigenesis were evaluated using the single cell gel electrophoresis (SCGE) assay and 2-stage carcinogenicity study, respectively. DNA damaged cells were markedly increased in the aryl hydrocarbon hydroxylase (AHH)-inducible mice, BALB/c and C57BL/6, as compared with the AHH-noninducible mice, DBA/2, in the SCGE assay. The AHH-inducible mice were more sensitive to DMBA than the AHH-noninducible mice in the 2-stage carcinogenicity study. These results strongly suggest that the genetic capacity to metabolize PAH is associated with the mutagenicity and carcinogenicity of DMBA.