Bioactivation, Mutagenicity, DNA Damage, and Oxidative Stress Induced by 3,4-Dimethylaniline.

3,4-Dimethylaniline (3,4-DMA) is present in cigarette smoke and widely used as an intermediate in dyes, drugs, and pesticides. Nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human CYP1A2 and N-acetyltransferase 1 (NAT1) alleles: (reference allele) or (the most common variant allele) were utilized to assess 3,4-DMA -acetylation and hypoxanthine phosphoribosyl transferase (HPRT) mutations, double-strand DNA breaks and reactive oxygen species (ROS). CHO cells expressing exhibited significantly ( < 0.001) higher 3,4-DMA -acetylation rates than CHO cells expressing both in vitro and in situ. In CHO cells expressing CYP1A2 and NAT1, 3,4-DMA caused concentration-dependent increases in reactive oxygen species (ROS), double-stranded DNA damage, and HPRT mutations. CHO cells expressing and exhibited concentration-dependent increases in ROS following treatment with 3,4-DMA (linear trend < 0.001 and < 0.0001 for and , respectively) that were lower than in CHO cells expressing CYP1A2 alone. DNA damage and oxidative stress induced by 3,4-DMA did not differ significantly ( >0.05) between CHO cells expressing and . CHO cells expressing showed higher HPRT mutants ( < 0.05) than CHO cells expressing . These findings confirm 3,4-DMA genotoxicity consistent with potential carcinogenicity.