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pubmed:abstractText |
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.
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