Immunochemical characterization and toxicological significance of P-450HFLb purified from human fetal livers.
Immunochemical properties of P-450HFLb purified from human fetal livers were investigated. P-450HFLb cross-reacted with antibodies to rat P-4501A1 but not with antibodies to CYP2A6, CYP2C9, CYP3A7 (P-450HFLa) and rat CYP2B1. In addition, P-450HFLb also cross-reacted with both monospecific antibodies to rat CYP1A1 and CYP1A2. However, P-450HFLb was shown to be an immunochemically distinct form of cytochrome P-450 from P-450PA (human CYP1A2). Immunoblot analysis of human fetal livers with the antibodies to P-450HFLb showed that P-450HFLb was expressed in all fetal livers studied although there appeared to be individual differences in the amounts of P-450HFLb expressed in fetal livers. The formation of mutagens from IQ (but not from AFB1) in fetal liver homogenates was inhibited by the antibodies to P-450HFLb in a dose dependent manner. These results suggest that P-450HFLb may be a form of human cytochrome P-450 classified into CYP1 gene family, and that the cytochrome P-450 is, in part, responsible for the mutagenic activation of IQ in human fetal livers as well as CYP3A7 (P-450HFLa).
Kitada
M
M
Hospital Pharmacy, Chiba University Hospital, Japan.
Kato
T
T
Ohmori
S
S
Kamataki
T
T
Itahashi
K
K
Guengerich
F P
FP
Rikihisa
T
T
Kanakubo
Y
Y
D016604:Aflatoxin B1 / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003429:Cross Reactions; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000502:physiology*; D005333:Fetus / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism; D051381:Rats
D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1