Journal article
Effects of polychlorinated biphenyls on cytochrome P450 induction in the chick embryo hepatocyte culture
Archives of biochemistry and biophysics, Vol.275(1), pp.252-262
1989
DOI: 10.1016/0003-9861(89)90371-8
PMID: 2510602
Abstract
The effects of pure synthetic polychlorinated biphenyl (PCB) congeners on the induction of cytochrome P450 and associated activities were examined in cultured chick embryo hepatocytes. Dose-response effects for the induction of total cytochrome P450, ethoxyresorufin-
O-deethylase (EROD) activity, and benzphetamine demethylase (BPDM) activity were studied using 10 selected tetra- to hexachlorinated PCB congeners. These studies revealed that PCBs caused effects in the chick hepatocyte culture different from previously observed effects in rat liver. Based on their effects in chick hepatocytes, the PCBs could be categorized into two groups. The first group (consisting of 3,3′,4,4′-PCB, 3,3′,4,4′,5-PCB, 3,3′,4,4′,5,5′-PCB, 2′,3,3′,4,5-PCB, 2,3,3′,4,4′,5′-PCB, and 2,3,4,4′,5-PCB) induced total cytochrome P450 2.4- to 2.9-fold and EROD activity from 1–2 pmol/min/mg protein to 162–247. There was marked variation in potency, but all these congeners had a maximal inducing dose above which cytochrome P450 concentrations and EROD activities declined. BPDM activities were increased only slightly (1.2- to 1.6-fold) at the maximal cytochrome P450 inducing dose. The second group of congeners (consisting of 2,2′,4,5,5′-PCB, 2,2′,4,4′,5,5′-PCB, and 2,2′,3,4,4′,6-PCB) induced total cytochrome P450 concentrations 4.0-fold and BPDM activities 2.2- to 2.6-fold with greatest activity occurring at the highest doses which could be added (10–50 μ
m). However, EROD activities were also increased by these congeners to 60–112 pmol/min/mg protein with declining activities seen at the highest PCB doses (i.e., resembling EROD induction patterns of the first group). The EROD induction patterns with these latter PCB congeners are noteworthy since these PCBs do not induce EROD activity in the rat. For both groups of PCB congeners, EROD induction was associated with increased accumulation of uroporphyrin in cultures exposed to exogenous 5-aminolevulinate. Studies investigating the reason for the depression of cytochrome P450 concentrations and/or EROD activities by high doses of the PCBs revealed that with the first group there was slightly decreased total protein synthesis, decreased total cell heme concentrations, and decreased accumulation of radiolabeled heme synthesized from 5-[
14C]aminolevulinate. These changes might represent nonspecific toxic effects of the first group of PCBs. However, since these changes were not seen with the second group of PCBs, it is unlikely that either inhibition of heme synthesis or toxicity cause the depression of EROD activity With high PCB doses.
Details
- Title: Subtitle
- Effects of polychlorinated biphenyls on cytochrome P450 induction in the chick embryo hepatocyte culture
- Creators
- Larry E Rodman - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506-0054, U.S.ASteven I Shedlofsky - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506-0054, U.S.AAlice T Swim - Department of Veterans Affairs Medical Center, Division of Gastroenterology, Lexington, Kentucky 40511 U.S.ALarry W Robertson - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506-0054, U.S.A
- Resource Type
- Journal article
- Publication Details
- Archives of biochemistry and biophysics, Vol.275(1), pp.252-262
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0003-9861(89)90371-8
- PMID
- 2510602
- ISSN
- 0003-9861
- eISSN
- 1096-0384
- Language
- English
- Date published
- 1989
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002574502771
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