The induction of alkoxyresorufin metabolism: a potential indicator of environmental contamination.
Methods of biochemical monitoring of individual animals for exposure to environmental contaminants are of great potential use. The hepatic metabolism of various alkoxyresorufins, which are highly specific substrates for certain forms of cytochrome(s) P450, is highly induced by a variety of environmental contaminants. Thus, the O-dealkylation of pentoxy- or benzyloxyresorufin was induced greater than 20-fold in the rat by alpha-hexachlorocyclohexane, 2,4,5,2',4',5'-hexabromobiphenyl, DDT and Aroclor-1254, while the metabolism of ethoxyresorufin was highly induced by 5,6-benzoflavone, 3,4,5,3',4',5'-hexabromobiphenyl and Aroclor-1254. Additionally, rats exposed to diets containing as little as 12 ppm DDT displayed greater than five-fold increases in the rate of hepatic O-dealkylation of benzyloxyresorufin. Induction of the hepatic metabolism of these resorufin ethers in 9000 xg supernatant fractions taken from rats exposed to potential environmental contaminants may constitute a valuable diagnostic indicator of the presence of a variety of pollutants, including polycyclic aromatic hydrocarbons, organochlorine pesticides, polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest the potential applicability of these substrates in detecting chemical contamination in the environment.
Lubet
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RA
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701.
Guengerich
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FP
Nims
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RW
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003640:Dealkylation; D004784:Environmental Monitoring / Q000379:methods; D004785:Environmental Pollutants / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010078:Oxazines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D004785:Environmental Pollutants; D010078:Oxazines; D003577:Cytochrome P-450 Enzyme System