DNA damage induced by 3,3 '-dimethoxybenzidine in liver and urinary bladder cells of rats and humans

3,3'-Dimethoxybenzidine (DMB), a congener of benzidine used in the dye indu stry and previously found to be carcinogenic in rats, was evaluated for its genotoxic activity in primary cultures of rat and human hepatocytes and of cells from human urinary bladder mucosa, as well as in liver and bladder m ucosa of intact rats. A similar modest dose-dependent frequency of DNA frag mentation was revealed by the alkaline elution technique in metabolically c ompetent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic DMB concentrations ranging from 56 to 180 mu M Replicating ra t hepatocytes displayed a modest increase in the frequency of micronucleate d cells after a 48-h exposure to 100 and 180 mu M concentrations. In primar y cultures of human urinary bladder mucosa cells exposed for 20 h to 100 an d 180 mu M DMB, the Comet assay revealed a clear-cut increase of DNA fragme ntation. In rats given one-half LD50 of DMB as a single oral dose, the GSH level was reduced in both the liver and urinary bladder mucosa, whereas DNA fragmentation was detected only in the bladder mucosa. Taken as a whole, t hese results suggest that DMB should be considered a potentially genotoxic chemical in both rats and humans; the selective effect on the rat urinary b ladder might be the consequence of pharmacokinetic behavior.