Xenobiotics and xenoestrogens in fish: modulation of cytochrome P450 and carcinogenesis.
As is the case with mammals, an ever-increasing number of cytochromes P450 (CYPs) are being characterized from fish. The focus of work on fish CYPs has been primarily on environmental induction of CYP1A by pollutants such as the polycyclic aromatic hydrocarbons, polychlorinated biphenyls, dioxins and dibenzofurans. This response has been the basis for a sensitive biomonitoring tool of ecosystem health for a number of years. Studies have documented a correlation between CYP1A induction, pollutant levels and tumor incidence, especially in bottom-dwelling species. The rainbow trout has been utilized as a tumor model to document the role of CYP1A modulation in the inhibition or promotion of cancer. Fish are also very responsive to the class of chemicals known as xenoestrogens. Recent evidence is presented documenting the modulation of CYPs by xenoestrogens and their potential role as modulators of the tumor response. In this paper, we summarize the current knowledge concerning the occurrence of CYPs in fish and focus on the role of CYP1A induction in environmental monitoring of various genotoxic carcinogens and in the modulation of cancer in the trout model. Finally, the important class of aquatic pollutants known as xenoestrogens have now been shown to modulate CYP levels perhaps leading to alterations in tumor response or other adverse effects.
Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis 97331-6602, USA. williamd@bcc.orst.edu
D E
DE
Williams
J J
JJ
Lech
D R
DR
Buhler
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004785:Environmental Pollutants / Q000494:pharmacology*; D004790:Enzyme Induction; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005399:Fishes / Q000378:metabolism*; D009153:Mutagens / Q000494:pharmacology; D009369:Neoplasms / Q000139:chemically induced / Q000662:veterinary*
D002273:Carcinogens; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System