Mutagenic activation of 2-amino-3-methylimidazo[4,5-f]quinoline by complementary DNA-expressed human liver P-450.
Eight forms of human liver microsomal P-450 were individually expressed in human hepatoma Hep G2 cells with a vaccinia virus cDNA expression system. Using the Ames test, each expressed P-450 was examined for its ability to activate to mutagenic products the compounds, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, respectively. Three forms of human P-450 significantly activated 2-amino-3-methylimidazo[4,5-f]quinoline when the latter was at high substrate concentrations, but only a single form, P-450IA2, showed very high activation of all promutagens at lower substrate concentrations. Human IA2 had extraordinarily high affinity towards four promutagens tested and is likely the predominant P-450 enzyme responsible for their mutagenic activation in human liver.
Aoyama
T
T
Laboratory of Molecular Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Gelboin
H V
HV
Gonzalez
F J
FJ
D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014616:Vaccinia virus
D009153:Mutagens; D011804:Quinolines; D011994:Recombinant Proteins; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA; D003577:Cytochrome P-450 Enzyme System