Oxidase activity, mixed function biphenyls

Melancon, M.J., C.R. Elcombe, M.J. Vodicnik and J.J. Lech. Induction of cytochromes P450 and mixed-function oxidase activity by polychlorinated biphenyls and beta-naphthoflavone in carp (Cyprinus carpio). Comp. Biochem. Physiol. 69C 219-226, 1981. 

Merrill JC, Beck DJ, Kaminski DA, et al. 1995. Polybrominated biphenyl of cytochrome P450 mixed function oxidase activity in primary rat and human heptocytes. Toxicology 33 147-153. 

We think that factors other than non-equilibrium conditions explain much of the departure from prediction of BCFs using Kg s. There Is evidence to suggest selective metabolism of chlorobiphenyls In certain species (14) and It has been shown that some species of fish and Crustacea contain mixed function oxidase activity that Is probably capable of metabolizing certain biphenyls at different rates (33). Furthermore, the mixed function oxidase activity In selected species of fish and Crustacea tested has been Induced to higher levels of activity by exposure to xenoblotlcs while, thus far, only low levels of activity can be demonstrated In bivalves (33). This Is Interesting as It Is consistent with our finding that the mixture of chlorobiphenyls In bivalves more closely approximates a mixture of Aroclors than does the mixture of chlorobiphenyls In lobster, crab and flounder. 

The mechanism is believed to involve metabolic activation in the kidney itself. Thus, when radiolabelled chloroform was given to mice, in the kidney the radiolabel was localized in the tubular cells which were necrotic. Certain microsomal enzyme inducers such as 3-methylcholanthrene decreased the nephrotoxicity but not hepatotoxicity of chloroform, and phenobarbital pretreatment had no effect on nephrotoxicity but increased hepatotoxicity. Pretreatment with polybrominated biphenyls, however, increased toxicity to both target organs and also increased mixed function oxidase activity in both. In vitro studies have shown that microsomal enzymemediated metabolism of chloroform to C02 occurs in... 

---