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.

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.