DNA ADDUCT FORMATION OF HEPATOCARCINOGENIC AROMATIC-AMINES IN RAT-LIVER - EFFECT OF CYTOCHROME-P450 INDUCERS

F344 rats were treated with an i.p. injection of amino-6-methyldipyrid o[1,2-alpha:3',2'-d]imidazole (Glu P-1) or 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and examined for the formation of the DNA adduct in the l iver. To examine the effect of pretreatment with a cytochrome p450 (CY P) inducer on the formation of DNA adduct, these rats were pretreated with 3-methylcholanthrene (MC; CYP1A1/1A2 inducer) or phenobarbital (P B; CYP2B inducer). Administration of Glu P-1 and 3-MeO-AAB gave 2 and 5 adducts, respectively as determined by P-32-postlabeling assay. By G lu P-1 administration, pretreatment of rats with MC, but not with PB, increased the total amount of DNA adducts including 3 new adducts as m inor products. In contrast, pretreatment of rats with PB increased the total amount of DNA adducts derived by 3-MeO-AAB. The increase of aro matic amine DNA adducts by pretreatment with a CYP inducer was proport ional to the activity of induced CYP isosyme(s) responsible for the mu tagenic activation of each aromatic amine.