PMID: 2118331Sep 1, 1990Paper

Chlorinated biphenyls induce cytochrome P450IA2 and uroporphyrin accumulation in cultures of mouse hepatocytes

Archives of Biochemistry and Biophysics
P R SinclairJ F Sinclair

Abstract

Previous enzymatic and immunological studies from this laboratory have indicated a critical role for cytochrome P450IA2-catalyzed uroporphyrinogen oxidation in the development of uroporphyria caused by halogenated aromatic hydrocarbons. To extend these studies, we investigated whether primary cultures of mammalian hepatocytes which are inducible for cytochrome P450IA2 are also inducible for chemically mediated uroporphyria. Hepatocytes were isolated from C57BL/6 mice and maintained on Matrigel, an extracellular matrix isolated from a mouse tumor. When these cultures were treated with 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 5-aminolevulinic acid (ALA), they accumulated cytochrome P450IA2 as well as uroporphyrin (URO) and heptacarboxyporphyrin for up to 12 days. Cultures treated with ALA alone accumulated no P450IA2 and very little URO. Neither URO accumulation nor the level of P450IA2 was affected by addition of iron as the nitrilotriacetate complex. Other inducers of P450IA2 in vivo (3,4,5,3',4'-pentachlorobiphenyl, 3,4,3',4'-tetrachlorobiphenyl, and 3-methylcholanthrene) also increased P450IA2 in the cultures and caused URO accumulation in the presence of added ALA. The tetrachlorobiphenyl and methylcholanthrene caused the...Continue Reading

References

Nov 15, 1989·Archives of Biochemistry and Biophysics·L E RodmanL W Robertson
Sep 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H L Bonkovsky
Mar 15, 1989·International Journal of Cancer. Journal International Du Cancer·A G SmithM M Manson
Jan 28, 1986·Biochemistry·H K KleinmanG R Martin
Jul 15, 1988·The Biochemical Journal·A J UrquhartJ A Sinclair
Mar 1, 1988·Journal of Cellular Physiology·E G SchuetzP S Guzelian
Jun 15, 1984·Toxicology and Applied Pharmacology·J B GreigA G Smith
Oct 1, 1981·Biochemical Pharmacology·J F SinclairH Bonkowsky
Jan 1, 1980·Annals of the New York Academy of Sciences·D M Bissell, P S Guzelian

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Citations

May 23, 2001·Archives of Biochemistry and Biophysics·P R SinclairJ F Sinclair
Apr 1, 1995·Journal of Bioenergetics and Biomembranes·G H Elder, A G Roberts
Jan 1, 1993·The International Journal of Biochemistry·L C XuE Bresnick
Feb 11, 1999·Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology & Endocrinology·N GormanP R Sinclair
Jan 16, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·J J SchlezingerJ J Stegeman
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·John D PhillipsJames P Kushner
Mar 1, 1993·Japanese Journal of Cancer Research : Gann·N Nemoto, J Sakurai
Mar 1, 1993·Japanese Journal of Cancer Research : Gann·N Nemoto, J Sakurai
Mar 7, 2006·Biochemical and Biophysical Research Communications·Mary Beth GenterHoward G Shertzer
Apr 23, 2005·Biochemical and Biophysical Research Communications·Peter GreavesAndrew G Smith
Aug 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P R SinclairR W Lambrecht
Mar 23, 2017·International Journal of Dermatology·Nancy S HandlerRobert A Schwartz
Mar 30, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kristina K WolfJacqueline F Sinclair
Jan 13, 2000·Toxicology and Applied Pharmacology·P R SinclairD W Nebert
Nov 8, 1996·Biochemical Pharmacology·D ConstantinA G Smith
May 1, 1992·Archives of Biochemistry and Biophysics·R W LambrechtJ F Sinclair

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