Evidence for the induction of cytochrome P‐452 in rat liver by Aroclor 1254, a commercial mixture of polychlorinated biphenyls

Borlakoglu, J.T.; Edwards-Webb, J. D.; Dils, R.; Wilkins, John P. G.; Robertson, Larry W.

doi:10.1016/0014-5793(89)81362-6

Cited by 14 publications

(2 citation statements)

References 6 publications

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“…The microsomal cytochrome-P-450-dependent components induced by PCB have similar relative molecular masses to microsomal fatty acid desaturases and have the same requirements for NADH : ferricytochromeb5 oxidoreductase, cytochrome b5, NADH or NADPH and molecular oxygen. This raises the intriguing question of whether specific forms of cytochrome P-450, in conjunction with NADPH -cytochrome-P-450 reductase, can desaturate fatty acids in addition to their well established role [21,281 in the hydroxylation of fatty acids.…”

Section: Discussionmentioning

confidence: 99%

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Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers

Borlakoglu

Edwards-Webb

Dils

1990

European Journal of Biochemistry

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1. Polychlorinated biphenyls (PCB) are abundant and persistent pollutants in the ecosystem. Commercial mixtures (e.g. Aroclor 1254) can contain up to 80 different isomers and congeners, many of which accumulate in biological systems by the ingestion of PCB-contaminated lipid components of food chains.2. Commercial mixtures of PCB induce, in hepatic microsomal membranes in vivo, a variety of different forms of the cytochrome P-450 components of enzyme systems involved in the metabolism of drugs and other xenobiotics, and can also induce the proliferation of this membrane. Since these microsomal enzyme systems share a number of the requirements of microsomal fatty acid desaturases, we have investigated whether the induction by PCB in vivo of cytochrome-P-450-linked enzymes in the proliferating hepatic microsomal membrane of the pigeon and the rat is accompanied by increased proportions of polyunsaturated fatty acids in t h s membrane.3. The most striking changes observed 120 h after treating pigeons and rats with 1.5 mmol Aroclor 1254/kg body mass were 2.2-fold and 1.6-fold increases, respectively, in the proportion of arachidonic acid in the hepatic microsomal membrane. When the effects of this treatment on the proliferation of this membrane and increase in liver mass are taken into account, the amount of arachidonic acid in the total microsomal membrane of pigeon and rat livers increased 6.7-fold and 1.9-fold, respectively.4. These changes were accompanied by very significant increases in pigeons and rats of the concentration of hepatic microsomal cytochrome P-450, and in the activity in microsomal protein of a wide range of cytochrome P-450-dependent enzyme involved in the metabolism of drugs and other xenobiotics.5. This effect of PCB, of increasing in vivo the degree of unsaturation of fatty acids of hepatic microsomal membrane, appears to be a novel finding, and does not seem to have been investigated for other drugs and xenobiotics. Preliminary results have shown that the effect is accompanied by substantial increases in the total activity of A s and A 5 microsomal fatty acid desaturases converting 18:2 (9, 12) (linoleic acid) to 20:4 (5, 8,11,14) (arachidonic acid) [Borlakoglu, J. T., Dils, R. R., Edwards-Webb, J. D. &Walker, C. H. (1988) Biochem. Soc. Trans. 16, 10721. 6. It is postulated that there is a significant link between increased fatty acid desaturation and the induction of cytochrome-P-450-linked enzymes, and this is discussed in terms of the mechanisms involved in the metabolism of foreign compounds.Polychlorinated biphenyls are abundant and persistent lipid-soluble pollutants in the ecosystem (see [1 -31 for reviews). Commercial mixtures (e.g. Aroclor 1254) may contain up to 80 different isomers and congeners, many of which accumulate in biological systems through ingestion of PCBcontaminated lipid components of food chains, and PCB are present in fatty tissues and blood of species at the apex of these chains [4, 51.

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Section: Discussionmentioning

confidence: 99%

“…Lauric acid 12-hydroxylase was measured by the formation of 12-hydroxylauric acid by capillary GC as described by Borlakoglu et al [21].…”

Section: Extraction Of Lipids and Analysis Ojtheirfutty Acid Composimentioning

confidence: 99%

Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers

Borlakoglu

Edwards-Webb

Dils

1990

European Journal of Biochemistry

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Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P450 inducers and peroxisome proliferating compounds

Dirven

Broek

Peters

et al. 1992

Biochemical Pharmacology

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Lactational transfer of 3,3′,4,4′-tetrachloro-and 2,2′,4,4′,5,5′-hexachlorobiphenyl induces cytochrome P450IVA1 in neonates

Borlakoglu

Clarke²,

Huang

et al. 1992

Biochemical Pharmacology

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Evidence for the induction of cytochrome P‐452 in rat liver by Aroclor 1254, a commercial mixture of polychlorinated biphenyls

Cited by 14 publications

References 6 publications

Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers

Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers

Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P450 inducers and peroxisome proliferating compounds

Lactational transfer of 3,3′,4,4′-tetrachloro-and 2,2′,4,4′,5,5′-hexachlorobiphenyl induces cytochrome P450IVA1 in neonates

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