Linked Life Data

1944239

Source:http://linkedlifedata.com/resource/pubmed/id/1944239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-12-19
pubmed:abstractText
The ability of 3,3',4,4'-tetrachlorobiphenyl to stimulate bilirubin degradation by liver microsomes from rats treated with a polycyclic aromatic hydrocarbon-type inducer has been confirmed and extended to another planar biphenyl, 3,3',4,4',5,5'-hexachlorobiphenyl. The following evidence indicates the involvement of an inducible cytochrome P450 isoenzyme in this reaction, with a role, specifically, for cytochrome P450IA1. (a) The biphenyl-dependent bilirubin degradation and 7-ethoxyresorufin O-deethylase (EROD) activity were both markedly inhibited by a monoclonal antibody raised against cytochrome P450IA1; the two dose-inhibition curves were essentially superimposable, with maximum inhibition observed for both activities at a ratio of antibody to total cytochrome P450 of about 1. (b) Treatment of rats with 3-methylcholanthrene increased both EROD activity and biphenyl-dependent bilirubin degradation not only in the liver (where both cytochromes P450IA1 and P450IA2 are inducible) but also in the kidney (where only induction of cytochrome P450IA1 has been reported), with similar ratios of the two enzymatic activities in both tissues. (c) With carbon tetrachloride and 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,4-dimethyl pyridine as selective suicide substrates of members of the cytochrome P450IA subfamily, the biphenyl-dependent degradation of bilirubin showed a good correlation with cytochrome P450IA1, determined both as EROD activity and as an immunoreactive band on immunoblotting. These findings implicate cytochrome P450IA1 in the alternative pathway of bilirubin disposal, which can be stimulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in Gunn rats, and also help substantiate the hypothesis that interaction of a polyhalogenated aromatic compound with the induced cytochrome may initiate an oxidative mechanism leading to oxidation of target molecules in the cell, one of which is bilirubin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
686-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Inducible bilirubin-degrading system of rat liver microsomes: role of cytochrome P450IA1.
pubmed:affiliation
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, United Kingdom.
pubmed:publicationType
Journal Article