6533b820fe1ef96bd127a674

RESEARCH PRODUCT

Evidence of chloroethylene oxide being the reactive metabolite of vinyl chloride towards DNA: comparative studies with 2,2′ -dichloro-diethylether

H. M. BoltR.j. LaibJ.g. FilserL.m. Gwinner

subject

Ethylene OxideMaleCancer ResearchVinyl CompoundsGuanineVinyl ChlorideEtherVinyl chlorideStructure-Activity Relationshipchemistry.chemical_compoundAnimalsChloroacetaldehydeTissue DistributionCarbon RadioisotopesBiotransformationCarcinogenEthanolProteinsRats Inbred StrainsDNAGeneral MedicineMetabolismRatsEthyl EthersKineticsLiverchemistryBiochemistryNucleic acidRNADNAProtein Binding

description

The roles of chloroethylene oxide (CEO) and chloroacetaldehyde (CAA) in carcinogenicity of vinyl chloride (VC) have been studied by comparing biological effects of VC exposure with those of 2,2'-dichlorodiethylether (bis(chloroethyl)ether, BCEE) as a metabolic precursor of CAA. Biological end-points investigated were covalent protein binding, nucleic acid (RNA and DNA) alkylation and the potency of the two chemicals to induce preneoplastic ATPase-deficient foci in rat liver. After exposure of rats to [1-14C]BCEE, BCEE derived radioactivity was bound to liver proteins. Analysis of hydrolysates of liver RNA and DNA gave no indication for the formation of either 7-N-(2-oxoethyl)guanine, 1,N6-ethenoadenine or 3,N4-ethenocytosine residues within the nucleic acids. After application of VC, BCEE or chloroethanol [CE), also a precursor of CAA) to young rats, only animals exposed to VC developed preneoplastic hepatocellular ATPase-deficient foci. From these investigations it is concluded, that CEO (which is not formed during metabolism of BCEE and CE), not CAA, is the ultimate carcinogenic principle in VC carcinogenicity.

yearjournalcountryeditionlanguage
1983-11-01Carcinogenesis
https://doi.org/10.1093/carcin/4.11.1483