Mutagenic activation of aflatoxin B1 by P-450 HFLa in human fetal livers.
The genotoxic and mutagenic activation of promutagens by human fetal livers was measured by the induction of umu gene expression in Salmonella typhimurium TA1535/pSk1002. Liver homogenates of human fetuses were the most active for the mutagenic activation of aflatoxin B1 (AFB1), followed by 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), and to a lesser extent by 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1). The amounts of P-450 HFLa immunochemically determined in human fetal livers correlated highly with the induction of umu gene expression by AFB1 (r = 0.98, n = 5). P-450 HFLa catalyzed the mutagenic activation of AFB1 in a reconstituted system: cytochrome b5 markedly stimulated the activation. Anti-P-450 HFLa antibodies inhibited the mutagenic activation of AFB1 in a dose-dependent manner. These results strongly support the idea that P-450 HFLa is responsible for the mutagenic activation of AFB1 in human fetal livers.
Kitada
M
M
Division of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Taneda
M
M
Ohi
H
H
Komori
M
M
Itahashi
K
K
Nagao
M
M
Kamataki
T
T
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D011804:Quinolines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D000348:Aflatoxins; D001426:Bacterial Proteins; D003573:Cytochrome b Group; D007093:Imidazoles; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1