Elcombe, CR; Franklin, RB; Lech, JJ
The polyhalogenated biphenyls are widespread and persistent environmental contaminants, and both the polychlorinated and polybrominated biphenyls have been found to accumulate in fish tissues. A pure polychlorinated biphenyl isomer, 2,2',5,5'-tetrachlorobiphenyl, was recently shown to possess a half-life of approximately 2 years in the rainbow trout, and certain higher chlorinated biphenyls are expected to have even longer tissue half-lives. The polychlorinated and polybrominated biphenyls are known to be potent inducers of mixed-function oxidase activity in several mammalian species. Crude mixtures of polychlorinated biphenyls, such as Aroclors® 1254 and 1242, exhibit enzyme-inducing properties that have been termed "mixed." That is, they appear to induce both cytochromes P-450 and P1-450 (P-448); these are classically associated with phenobarbital-and 3-methylcholanthrene-induction, respectively. Crude polybrominated biphenyls also appear to induce forms of cytochrome(s) P-450 that exhibit "mixed" properties.
Much work has demonstrated the presence of multiple forms of hemoproteins P-450 in hepatic microsomes of rats, mice, and rabbits. It has further been shown that the relative proportions of these isoenzymes may be altered considerably by various
chemical agents. These variations in hemoprotein(s) P-450 subpopulations may lead to distinct changes in the metabolic pathways of chemicals.
More recently, attention has been directed to the potential of other species to metabolize foreign compounds. Of particular concern has been the ability of fish to metabolize xenobiotics. Early work suggested a lack of drug-metabolizing enzymes in aquatic species; however, it is now recognized that fish do indeed possess an array of drug-metabolizing enzymes comparable in many respects to those found in mammals. Induction of hemoprotein(s) P-450-mediated monooxygenase activity has been demonstrated in fish by using agents such as the polycyclic aromatic hydrocarbons, crude petroleum, and the polyhalogenated biphenyls. Compounds such as 2,3-benzanthracene and, 8-naphthoflavone not only increase the metabolism of model mixed-function oxidase substrates in vitro but also increase the in vivo metabolism and disposition of various chemicals. Recently, reports have appeared indicating that fish possess multiple forms of hepatic microsomal hemoprotein(s) P-450 and that treatment of fish with polycyclic aromatic hydrocarbons or polychlorinated biphenyls results in an alteration of the hemoprotein(s) P-450 subpopulations.
The present paper compares the effect of polychlorinated-and polybrominated biphenyls on the hepatic microsomal hemoprotein(s) P-450 and the monooxygenase systems of rainbow trout and rats.