Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
1984-6-25
|
pubmed:abstractText |
1,2-Dichloroethane, 1,1,1-trichloroethane and 1,1,2,2-tetrachloroethane appear to be metabolized by hepatic nuclear cytochrome P-450. All of these compounds are converted to chlorinated metabolites after incubation with hepatic nuclei and an NADPH-generating system plus EDTA, with the omission of any component eliminating metabolite production. In addition, CO, an inhibitor of cytochrome P-450, diminished the production of the chlorinated metabolites by hepatic nuclear preparations. The major metabolites of the chlorinated ethanes from hepatic microsomal cytochrome P-450, viz. chloroacetaldehyde from 1,2-dichloroethane, 2,2,2-trichloroethanol from 1,1,1-trichloroethane, and dichloroacetic acid from 1,1,2,2-tetrachloroethane, were also produced from the three chloroalkanes by hepatic nuclear cytochrome P-450. The levels of the metabolites produced were 65, 0.09 and 4.4 nmol/nmol cytochrome P-450/60 min. It is proposed that the pathways for the formation of these metabolites by hepatic nuclear cytochrome P-450 are as for their production by hepatic microsomal cytochrome P-450. Chloral hydrate was produced from 1,1,1-trichloroethane by hepatic nuclei plus NADPH, but not by hepatic microsomes. The presence of reactive species or transient enzyme bound intermediates in the pathways for the cytochrome P-450 dependent metabolism of the chloroethanes in hepatic nuclei is suggested by the observation that nuclear cytochrome P-450 is degraded in the presence of the chloroethanes in a NADPH dependent process which is inhibited by CO. It is proposed that, although the cytochrome P-450 dependent metabolism of the chloroethanes in microsomes can greatly exceed that in nuclei, the metabolism of 1,2-dichloroethane and 1,1,2,2-tetrachloroethane by nuclear cytochrome P-450 may in part mediate the mutagenicity and carcinogenicity of parent compounds.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,1,1-trichloroethane,
http://linkedlifedata.com/resource/pubmed/chemical/1,1,2,2-tetrachloroethane,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Ethane,
http://linkedlifedata.com/resource/pubmed/chemical/Ethylene Dichlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocarbons, Chlorinated,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Trichloroethanes,
http://linkedlifedata.com/resource/pubmed/chemical/ethylene dichloride
|
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0143-3334
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
5
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
543-8
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:6722974-Animals,
pubmed-meshheading:6722974-Biotransformation,
pubmed-meshheading:6722974-Cell Fractionation,
pubmed-meshheading:6722974-Cell Nucleus,
pubmed-meshheading:6722974-Cytochrome P-450 Enzyme System,
pubmed-meshheading:6722974-Ethane,
pubmed-meshheading:6722974-Ethylene Dichlorides,
pubmed-meshheading:6722974-Hydrocarbons, Chlorinated,
pubmed-meshheading:6722974-Kinetics,
pubmed-meshheading:6722974-Liver,
pubmed-meshheading:6722974-Male,
pubmed-meshheading:6722974-Microsomes, Liver,
pubmed-meshheading:6722974-Phenobarbital,
pubmed-meshheading:6722974-Rats,
pubmed-meshheading:6722974-Trichloroethanes
|
pubmed:year |
1984
|
pubmed:articleTitle |
Metabolism of chloroethanes by rat liver nuclear cytochrome P-450.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|