beta-Naphthoflavone-inducible cytochrome P4501A1 activity in liver microsomes of the marine safi fish (Siganus canaliculatus).
The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics has been investigated in liver microsomes prepared from a local marine safi fish, Siganus canaliculatus. The safi fish was found to have a well-developed microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NADPH-cytochrome c reductase. The fish microsomal enzyme system was able to metabolize benzo(a)pyrene, 7-ethoxycoumarin and 7-ethoxyresorufin. Male fish were found to exhibit a higher monooxygenase activity than female fish. Treatment of fish with beta-naphthoflavone was found to induce (2- to 4-fold) the activities of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase. HPLC analysis of the metabolites produced by incubation of benzo(a)pyrene with the liver microsomal preparation showed a predominant formation of 3-OH and 9-OH benzo(a)pyrene. There was an increased formation of benzo(a)pyrene 7,8-diol and benzo(a)pyrene 7,8,9,10-tetrol in liver microsomes prepared from beta-naphthoflavone-treated fish. Western immunoblot analysis of liver microsomes from beta-naphthoflavone-treated fish using an antibody to rat liver cytochrome P4501A1 (CYP1A1) suggested the presence of an inducible cytochrome P450 enzyme that was comparable with that of rat liver enzyme. Our results suggest that liver microsomes from the safi fish have multiple forms of cytochrome P450 with a specific beta-naphthoflavone-inducible CYP1A1 homologous protein that can metabolize a variety of substrates.
Raza
H
H
Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Otaiba
A
A
Montague
W
W
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D004790:Enzyme Induction; D005260:Female; D005399:Fishes / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011083:Polycyclic Compounds / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002273:Carcinogens; D007527:Isoenzymes; D011083:Polycyclic Compounds; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System