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/c X DBA/2)F1 (CDF1) mice of both sexes were treated for 1 week with a dietary hepatocarcinogenic tryptophan pyrolysate component (Trp P-1 or Trp P-2), and the activity of hepatic microsomal enzyme(s) for mutagenic activations of Trp P-1 and Trp P-2 were assessed by means of a mutation test with Salmonella typhimurium TA98. In both Ah-responsive (BALB/c and CDF1) and Ah-nonresponsive (DBA/2) mice, the dietary treatment with Trp P-1 or Trp P-2 resulted in a significant increase of the enzyme activity for mutagenic activations of Trp P-1 and Trp P-2 in females but not in males, except the case of male BALB/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 to be cytochrome P-450 isozyme(s) (mol. wt of 55,000 daltons) by immunoblots with use of an anti-rat cytochrome P-448 monoclonal antibody and by selective inhibition of the activity by addition of 7,8-benzoflavone into the mutation assay system. These findings indicate that carcinogenic aromatic amines such as Trp P-1 and Trp P-2 are able to induce hepatic cytochrome P-450 isozyme(s) not only in Ah-responsive mice (BALB/c and CDF1) but also in Ah-nonresponsive DBA/2 mice and that the cytochrome P-450 induction is controlled by androgen(s).
Degawa
M
M
Department of Hygienic Chemistry, Tohoku University, Sendai, Japan.
Yamaya
C
C
Hashimoto
Y
Y
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D003433:Crosses, Genetic; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004032:Diet; D004790:Enzyme Induction; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D012016:Reference Values; D012737:Sex Factors; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology
D002243:Carbolines; D002273:Carcinogens; D007527:Isoenzymes; D013739:Testosterone; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D003577:Cytochrome P-450 Enzyme System; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole