Hepatocarcinogenic heterocyclic aromatic amines that induce cytochrome P-448 isozymes, mainly cytochrome P-448H (P-450IA2), responsible for mutagenic activation of the carcinogens in rat liver.
Male F344 rats were treated with hepatocarcinogenic heterocyclic aromatic amines such as amino acid- and protein-pyrolysate components (Trp P-1, Trp P-2, Glu P-1, Glu P-2, A alpha C, MeA alpha C, IQ and MeIQx) and changes in microsomal cytochrome P-450 isozymes in the livers were examined by means of immuno-Western blotting using anti-rat cytochrome P-450 monoclonal antibodies. The results suggested that all chemicals tested induce cytochrome P-448 isozymes, particularly cytochrome P-448H (P-450IA2), which efficiently mediate mutagenic activation of the carcinogens. This was substantiated by the enzymatic analyses with the substrates showing different characters to rat cytochrome P-450 isozyme-mediated mutagenesis.
Degawa
M
M
Department of Hygienic Chemistry, Pharmaceutical Institute, Tohoku University, Sendai, Japan.
Tanimura
S
S
Agatsuma
T
T
Hashimoto
Y
Y
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System