TY - JOUR
T1 - Evidence of chloroethylene oxide being the reactive metabolite of vinyl chloride towards DNA
T2 - Comparative studies with 2,2' -dichloro-diethylether
AU - Gwinner, L. M.
AU - Laib, R. J.
AU - Filser, J. G.
AU - Bolt, H. M.
N1 - Funding Information:
The financial support of the 'Deutsche Forschungsgemeninschaft', Bo 491/6-2, is gratefully acknowledged.
PY - 1983/11
Y1 - 1983/11
N2 - 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 chloro-ethanol ((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.
AB - 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 chloro-ethanol ((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.
UR - http://www.scopus.com/inward/record.url?scp=0021075566&partnerID=8YFLogxK
U2 - 10.1093/carcin/4.11.1483
DO - 10.1093/carcin/4.11.1483
M3 - Article
C2 - 6196138
AN - SCOPUS:0021075566
SN - 0143-3334
VL - 4
SP - 1483
EP - 1486
JO - Carcinogenesis
JF - Carcinogenesis
IS - 11
ER -
