Abstract
FireMaster BP-6 is a commercial polybrominated biphenyl (PBB) preparation containing a complex mixture of isomers with the major component being identified as 2,2',4,4',5,5'-hexabromobiphenyl. Column chromatographic techniques have been developed in which the crude FireMaster is separated into three fractions, F1, F2, and F3, in increasing order of polarity. F1 consists of highly purified 2,2',4,4',5,5'-hexabromobiphenyl (94%) whereas F2-F3 contain less of this isomer and correspondingly more of the other bromobiphenyl components. Previously we have shown that crude FireMaster BP-6 is metabolized in mammals to give hydroxylated degradation products and the metabolism of F1, not unexpectedly, gives comparable results. It is well known that PBBs are effective inducers of diverse microsomal enzymes including including the aryl hydrocarbon hydroxylase (AHH) system. The effects of FireMaster BP-6 and F1-F3 as AHH inducers have been investigated by using the following approach: the substrates used to monitor AHH activity are model halogenated aromatic compounds; the levels of metabolites and metabolite conjugates formed have been quantitated for control and induced enzymes; the levels of macromolecular adducts have also been quantitated for the inducers. This approach thus not only measures the rate of increase of detoxification products (metabolites and metabolite conjugates) but also monitors the macromolecule adduct formation which represents a toxification route. The effects of the PBBs as AHH inducers will be discussed in terms of the above approach.
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- Alvares A. P., Bickers D. R., Kappas A. Polychlorinated biphenyls: a new type of inducer of cytochrome P-448 in the liver. Proc Natl Acad Sci U S A. 1973 May;70(5):1321–1325. doi: 10.1073/pnas.70.5.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dent J. G., Netter K. J., Gibson J. E. The induction of hepatic microsomal metabolism in rats following acute administration of a mixture of polybrominated biphenyls. Toxicol Appl Pharmacol. 1976 Nov;38(2):237–249. doi: 10.1016/0041-008x(76)90132-0. [DOI] [PubMed] [Google Scholar]
- Heidelberger C. Chemical carcinogenesis. Annu Rev Biochem. 1975;44:79–121. doi: 10.1146/annurev.bi.44.070175.000455. [DOI] [PubMed] [Google Scholar]
- Kay K. Polybrominated biphenyls (PBB) environmental contamination in Michigan, 1973-1976. Environ Res. 1977 Feb;13(1):74–93. doi: 10.1016/0013-9351(77)90006-8. [DOI] [PubMed] [Google Scholar]
- OMURA T., SATO R. THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. J Biol Chem. 1964 Jul;239:2370–2378. [PubMed] [Google Scholar]
- Pietropaolo C., Weinstein I. B. Binding of [3H]benzo(a)pyrene to natural and synthetic nucleic acids in a subcellular microsomal system. Cancer Res. 1975 Aug;35(8):2191–2198. [PubMed] [Google Scholar]
- Safe S., Jones D., Hutzinger O. Metabolism of 4,4'-dihalogenobiphenyls. J Chem Soc Perkin 1. 1976;(4):357–359. [PubMed] [Google Scholar]
- Stonard M. D. Mixed type hepatic microsomal enzyme induction by hexachlorobenzene. Biochem Pharmacol. 1975 Nov 1;24(21):1959–1963. doi: 10.1016/0006-2952(75)90382-2. [DOI] [PubMed] [Google Scholar]