Possible occurrence of P450 related to P450 HFLb in extrahepatic tissues of human fetuses and its contribution to metabolic activation of promutagens.
P450 HFLb purified from human fetal livers has been shown to be constitutively expressed in fetal livers. In the present study, the occurrence of proteins immunochemically related to P450 HFLb in extrahepatic tissues of human fetuses and their contribution to mutagenic activation of promutagens were investigated. The mutagenic activation of aflatoxin B1 (AFB1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and benzo[a]pyrene were observed in human fetal extrahepatic tissues, including adrenal glands, kidneys and lungs, at varying rates. Immunoblot analysis of homogenates of extrahepatic tissues with antibodies to P450 HFLb revealed the occurrence of proteins immunochemically related to P450 HFLb in adrenal glands, kidneys and lungs. Immuno-inhibition studies suggested that in fetal adrenal gland and kidney, the proteins cross-reactive with antibodies to P450 HFLb were capable of activating IQ and MeIQ to mutagens.
Kato
T
T
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Nakasa
H
H
Ohmori
S
S
Kamataki
T
T
Itahashi
K
K
Shimada
T
T
Rikihisa
T
T
Kitada
M
M
D000311:Adrenal Glands / Q000201:enzymology / Q000378:metabolism; D016604:Aflatoxin B1 / Q000493:pharmacokinetics; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005333:Fetus / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D009153:Mutagens / Q000493:pharmacokinetics*; D011804:Quinolines / Q000493:pharmacokinetics
D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline