Hepatic monooxygenase induction and promutagen activation in channel catfish from a contaminated river basin

Abstract

To better understand the etiology of cancer in fish from polluted waters, the impact of environmental contaminants on xenobiotic metabolism of channel catfish ( Ictalurus punctatus) from a highly polluted water body, Devil's Swamp in southeastern Louisiana, has been investigated. Fish from Devil's Swamp bioaccumulated polynuclear aromatic hydrocarbons (PAH), chlorinated hydrocarbon insecticides (CHI), and polychlorinated biphenyls (PCB) in fat tissue, the latter exceeding 7000 ppb. Reference catfish from the University farm, Ben Hur, were virtually devoid of PAH, CHI, and PCB. Liver microsomal enzymes (MFO) from Devil's Swamp fish were markedly induced. The specific content of cytochromes P450 and b 5 and the specific activities of NAD(P)H-cytochrome c reductase were two to three times higher than those of Ben Hur fish. Consistent with this induction, a 9000 g supernatant from Devil's Swamp but not Ben Hur fish activated 2-aminofluorene and benzo[ a]pyrene (BP) to mutagens in the Ames test. BP metabolism by Devil's Swamp fish liver microsomes was inhibited to a greater extent by α-naphthoflavone than was BP metabolism by Ben Hur fish microsomes. This finding indicates that the induced activity in the Devil's Swamp fish liver was the result of P450 isozymes characteristic of PAH/PCB induction. Thus, exposure of fish to environmental pollutants can alter MFO leading to enhanced metabolic activation of promutagens to mutagens.