Metabolism of chloroethanes by rat liver nuclear cytochrome P-450

1, 2-DichJoroethane, 1, 1, 1-trichloroethane and 1, 1, 2, 2-tetra-chloroethane appear to be metabolized by hepatic nudear 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...

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Published in:Carcinogenesis (New York) 1984-05, Vol.5 (5), p.543-548
Main Authors: Casdola, Livia A.F., Ivanetich, Kathryn M.
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description 1, 2-DichJoroethane, 1, 1, 1-trichloroethane and 1, 1, 2, 2-tetra-chloroethane appear to be metabolized by hepatic nudear 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 nudear preparations. The major metabolites of the chlorinated ethanes from hepatic mtcrosomal cytochrome P-450, viz. chloroacetaldehyde from 1, 2-dichloroethane, 2, 2, 2-trichloroethanol from 1, 1, 1-trichloroethane, and dichloroacetic add from 1, 1, 2, 2-tetrachloroethane, were also produced from the three chloroaikanes by hepatic nudear 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 nudear 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 nudei 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 nudei 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 nudei, the metabolism of 1, 2-dichloroethane and 1, 1, 2, 2-tetrachloroethane by nudear cytochrome P-450 may in part mediate the mutagenidty and carcinogenidty of parent compounds.
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Ivanetich, Kathryn M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-8bf0f84ae7b59cca74e37d91e0d6fa516a97ef656aa1eebb90769b0d9fd556bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1984</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Cell Fractionation</topic><topic>Cell Nucleus - metabolism</topic><topic>Chemical agents</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Ethane - analogs &amp; derivatives</topic><topic>Ethane - metabolism</topic><topic>Ethylene Dichlorides - metabolism</topic><topic>Hydrocarbons, Chlorinated - metabolism</topic><topic>Kinetics</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microsomes, Liver - metabolism</topic><topic>Phenobarbital - pharmacology</topic><topic>Rats</topic><topic>Trichloroethanes - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Casdola, Livia A.F.</creatorcontrib><creatorcontrib>Ivanetich, Kathryn M.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Pollution Abstracts</collection><collection>Safety Science and Risk</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Casdola, Livia A.F.</au><au>Ivanetich, Kathryn M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism of chloroethanes by rat liver nuclear cytochrome P-450</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>1984-05</date><risdate>1984</risdate><volume>5</volume><issue>5</issue><spage>543</spage><epage>548</epage><pages>543-548</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>1, 2-DichJoroethane, 1, 1, 1-trichloroethane and 1, 1, 2, 2-tetra-chloroethane appear to be metabolized by hepatic nudear 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 nudear preparations. The major metabolites of the chlorinated ethanes from hepatic mtcrosomal cytochrome P-450, viz. chloroacetaldehyde from 1, 2-dichloroethane, 2, 2, 2-trichloroethanol from 1, 1, 1-trichloroethane, and dichloroacetic add from 1, 1, 2, 2-tetrachloroethane, were also produced from the three chloroaikanes by hepatic nudear 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 nudear 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 nudei 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 nudei 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 nudei, the metabolism of 1, 2-dichloroethane and 1, 1, 2, 2-tetrachloroethane by nudear cytochrome P-450 may in part mediate the mutagenidty and carcinogenidty of parent compounds.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>6722974</pmid><doi>10.1093/carcin/5.5.543</doi><tpages>6</tpages></addata></record>
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source Oxford University Press:Jisc Collections:Oxford Journal Archive: Access period 2024-2025
subjects Animals
Biological and medical sciences
Biotransformation
Carcinogenesis, carcinogens and anticarcinogens
Cell Fractionation
Cell Nucleus - metabolism
Chemical agents
Cytochrome P-450 Enzyme System - metabolism
Ethane - analogs & derivatives
Ethane - metabolism
Ethylene Dichlorides - metabolism
Hydrocarbons, Chlorinated - metabolism
Kinetics
Liver - drug effects
Liver - metabolism
Male
Medical sciences
Microsomes, Liver - metabolism
Phenobarbital - pharmacology
Rats
Trichloroethanes - metabolism
Tumors
title Metabolism of chloroethanes by rat liver nuclear cytochrome P-450
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