Date of Award

6-1996

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

Dr. Haider Raza

Second Advisor

Dr. Badrulddin Ali

Third Advisor

H.H. Sidique

Abstract

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 caught from the Arabian Gulf of United Arab Emirates. The Safi fish was found to have a well developed liver microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NADPH-cytochrome c reductase. The fish microsomal enzyme system was able to metabolise 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 β-naphthoflavone was found to induce (2-4 fold) the activities of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase. In vitro addition of α-naphthoflavone, a specific inhibitor of β-naphthoflavone inducible cytochrome P450s activities was found to inhibit the enzyme activities. These findings suggest the presence of various forms of cytochrome P450 in Safi fish liver.

Western immunoblot analysis of liver microsomes from β-naphthoflavone treated fish using an antibody to rat liver cytochrome P450 1A1 (CYP1A1) suggested the presence of an inducible cytochrome P450 enzyme which was homologous to the mammalian CYP1A1 and 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 β-naphtho-flavone inducible CYP1A 1 homologous protein that can metabolise a variety of carcinogenic and non-carcinogenic substrates. Our results also indicate that like rats and mice and some other marine fish, Safi fish could also be used as a sensitive tool for the monitoring of the Arabian Gulf region pollution, especially with polycyclic hydrocarbons of the coastal water.

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