the mutagenicity , metabolism , dna adduction and induction of unscheduled dna synthesis ( uds ) of 1-nitropyrene and 1,8-dinitropyrene were investigated in the human hepatoma cell line hepg2 . 
 previous results had demonstrated that 1-nitropyrene was both mutagenic at the hgprt locus and induced uds in these cells . in the present study , we find that the dinitropyrenes , although highly mutagenic in salmonella typhimurium , are not mutagenic and do not induce uds in the hepg2 . 
 although the rate of 1,8-dinitropyrene nitroreduction was less than that of 1-nitropyrene nitroreduction , this did not explain the lack of mutagenicity and uds induction by the dinitropyrenes . 
 therefore , it is proposed that the arylhydroxylamine o - esterificase is not expressed in these cells . 
 since cytochrome p450-mediated c - oxidation is the predominant metabolic pathway in vivo , we sought to determine if an increase in the ratio of cytochrome p450-mediated c - oxidation over nitroreduction would result in increased or decreased dna adducts in the hepg2 . 
 the administration of 2.5 microm 3-methylcholanthrene to the hepg2 increased the ratio of c - oxidation / nitroreduction from 2.8 + /- 
 1.9 to 50.4 + /- 
 46.1 . 
 this was accompanied by a decrease in the c8-guanyl adduct of 1-nitropyrene ( via nitroreduction ) from 18.7 + /- 
 7.0 to 4.8 + /- 
 1.7 fmoles / micrograms dna , without any further increase in other 1-nitropyrene dna adducts . 
 these results suggest that the cytochrome p450-mediated metabolism of 1-nitropyrene to epoxides , phenols , and dihydrodiols is not an activation pathway in the hepg2 cells , and may explain the weak carcinogenicity of 1-nitropyrene in vivo , where cytochrome p450-mediated c - oxidation predominates.imagesfigure 4 .