Home LiteratureArticle Details

PMID: 6412692 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria.

The Biochemical journal ·Vol. 214 ·No. 1 ·1983-07-15 ·Pages 145-51

De Verneuil H, Sassa S, Kappas A

Abstract

Treatment of cultured chick embryo hepatocytes with phenobarbital, polychlorinated biphenyl compounds and 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased delta-aminolaevulinate synthase and decreased uroporphyrinogen decarboxylase activities and porphyrin accumulation; uroporphyrin and heptacarboxyporphyrin predominated. Iron had no effect on these changes. Simultaneous treatment of cultures with dioxin and phenobarbital produced a synergistic response in delta-aminolaevulinate synthase induction, uroporphyrinogen decarboxylase inhibition and porphyrin accumulation. These data suggest that an inhibitor of uroporphyrinogen decarboxylase may be generated in the liver from polychlorinated biphenyl compounds or dioxin by metabolic activation. Additionally these findings bear on the postulated role of these and related chemicals in determining the low levels of uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients.

MeSH Terms

5-Aminolevulinate Synthetase/metabolism Animals Benzoflavones/pharmacology Carboxy-Lyases/antagonists & inhibitors Cells, Cultured Chick Embryo Chromatography, High Pressure Liquid Dioxins/pharmacology Iron/pharmacology Liver/drug effects,enzymology Phenobarbital/pharmacology Polychlorinated Biphenyls/pharmacology Polychlorinated Dibenzodioxins/pharmacology Porphyrias/enzymology Porphyrins/metabolism Uroporphyrinogen Decarboxylase/antagonists & inhibitors beta-Naphthoflavone

Chemicals

Benzoflavones Dioxins Polychlorinated Dibenzodioxins Porphyrins beta-Naphthoflavone Polychlorinated Biphenyls Iron 5-Aminolevulinate Synthetase Carboxy-Lyases Uroporphyrinogen Decarboxylase Phenobarbital

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

De Verneuil H

Sassa S

Kappas A

References (23)

23 references, click to expand

Relative abilities on a molar basis of hexafluoro-, hexachloro- and hexabromobenzenes to decrease liver uroporphyrinogen decarboxylase activity and cause porphyria in female rats.
Res Commun Chem Pathol Pharmacol. 1980 May;28(2):377-84 PMID: 7394329
Activation of uroporphyrinogen decarboxylase by ferrous iron in porphyria cutanea tarda.
S Afr Med J. 1979 Nov 24;56(22):918-20 PMID: 515872
Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase.
Biochem Biophys Res Commun. 1981 Nov 16;103(1):264-71 PMID: 6459093
Decreased hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda.
N Engl J Med. 1982 Apr 1;306(13):766-9 PMID: 7062951
Purification and properties of uroporphyrinogen decarboxylase from human erythrocytes. A single enzyme catalyzing the four sequential decarboxylations of uroporphyrinogens I and III.
J Biol Chem. 1983 Feb 25;258(4):2454-60 PMID: 6822570
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
Decreased uroporphyrinogen decarboxylase activity in 'experimental symptomatic porphyria'.
Life Sci II. 1971 Aug;10(15):887-93 PMID: 4105367
Comparative toxicologic study with polychlorinated biphenyls in chickens with special reference to porphyria, edema formation, liver necrosis, and tissue residues.
Toxicol Appl Pharmacol. 1970 Nov;17(3):656-68 PMID: 5495989
Nervous and biochemical disturbances following hexachlorobenzene intoxication.
Nature. 1961 Jul 22;191:363-6 PMID: 13720711
Hepatic porphyria induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse.
Res Commun Chem Pathol Pharmacol. 1973 Nov;6(3):919-28 PMID: 4760898
Experimental hepatic porphyria induced by polychlorinated biphenyls.
Toxicol Appl Pharmacol. 1974 Feb;27(2):437-48 PMID: 4211999
Uroporphyrin formation induced by chlorinated hydrocarbons (lindane, polychlorinated biphenyls, tetrachlorodibenzo-p-dioxin). Requirements for endogenous iron, protein synthesis and drug-metabolizing activity.
Biochem Biophys Res Commun. 1974 Nov 6;61(1):124-33 PMID: 4140722
The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase.
J Clin Invest. 1975 Sep;56(3):661-7 PMID: 1159079
The effect of the porphyrogenic compound, hexachlorobenzene, on the activity of hepatic uroporphyrinogen decarboxylase in the rat.
Clin Sci Mol Med. 1976 Jul;51(1):71-80 PMID: 939068
An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity.
J Clin Invest. 1976 Nov;58(5):1089-97 PMID: 993332
Induction of aminolevulinate synthase and porphyrins in cultured liver cells maintained in chemically defined medium. Permissive effects of hormones on induction process.
J Biol Chem. 1977 Apr 10;252(7):2428-36 PMID: 321458
Two methods for determining the activity of delta-aminolevulinate synthetase within intact liver cells in culture.
Anal Biochem. 1977 May 1;79(1-2):380-93 PMID: 405884
Association between induction of aryl hydrocarbon hydroxylase and depression of uroporphyrinogen decarboxylase activity.
Res Commun Chem Pathol Pharmacol. 1977 Aug;17(4):631-7 PMID: 897351
Induction of porphyrin synthesis in chick embryo liver cell culture by synthetic polychlorobiphenyl isomers.
Biochim Biophys Acta. 1978 Apr 19;540(1):83-92 PMID: 416856
Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda.
N Engl J Med. 1978 Aug 10;299(6):274-8 PMID: 661926
Familial and sporadic porphyria cutanea: two different diseases.
Hum Genet. 1978 Oct 31;44(2):145-51 PMID: 730158
Hormonal requirements for the induction of cytochrome P-450 in hepatocytes cultured in a serum-free medium.
Biochem Biophys Res Commun. 1979 Feb 14;86(3):710-7 PMID: 570840
Polychlorobiphenyls that induce delta-aminolevulinic acid synthetase inhibit uroporphyrinogen decarboxylase in cultured chick embryo liver cells.
FEBS Lett. 1981 Jun 29;129(1):93-6 PMID: 6791968

Article Info

Journal

The Biochemical journal

Abbr.

Biochem J

ISSN

0264-6021

DOI

10.1042/bj2140145

Published

1983-07-15

Pages

145-51

Language

English

Region

England

NLM ID

2984726R

PMCID

PMC1152219

Subset

Grants

NIEHS NIH HHS · ES-01055 · United States

External Links

PubMed source DOI: 10.1042/bj2140145 PMC Full Text View journal details

Analysis Services

Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria.

Contact

WeChat Official Account