Hepatic cytochrome P-450 isozyme(s) induced by dietary carcinogenic aromatic amines preferentially in female mice of DBA/2 and other strains

DBA/2, BALB/c or (BALB/cxDBA/2)F₁ (CDF₁) mice of both sexeswere treated for 1 week with a dietary hepatocarcinogenic tryptophanpyrolysate component (Trp P-1 or Trp P-2), and the activityof hepatic microsomal enzyme(s) for mutagenk activations ofTrp P-1 and Trp P-2 were assessed by means of a mutation testwith Salmonella typhimurium TA98. In both Ah-responsive (BALB/cand CDF₁) and Ah-nonresponsive (DBA/2) mice, the dietary treatmentwith Trp P-l or Trp P-2 resulted in a significant increase ofthe enzyme activity for mutagenic activations of Trp P-1 andTrp P-2 in females but not in males, except the case of maleBALB/c mice treated with dietary Trp P-1 Also induction of enzyme(s)in female mice was suppressed by an administration of testosterone.The induced hepatic microsomal enzyme(s) was demonstrated tobe cytochrome P-450 isozyme(s) (mol. wt of 55 000 daltons) byimmunoblots with use of an anti-rat cytochrome P-448 monoclonalantibody and by selective inhibition of the activity by additionof 7,8-benzoflavone into the mutation assay system. These findingsindicate that carcinogic aromatic amines such as Trp P-1 andTrp P-2 are able to induce hepatic cytochrome P-450 isozyme(s)not only in Ah-responsive mice (BALB/c and CDF₁) but also inAh-nonresponsive DBA/2 mice and that the cytochrome P-450 inductionis controlled by androgen(s).