DNA alkylation by vinyl chloride metabolites: etheno derivatives or 7-alkylation of guanine?
The state of the literature led to a re-investigation of the alkylation products caused by vinyl chloride metabolites in DNA. When rat liver microsomes, an NADPH-regenerating system, DNA and [14C]vinyl chloride were incubated and, when the DNA was subsequently re-isolated and (enzymatically) hydrolyzed, chromatograms (on Aminex A-6) showed the presence of 1,N6-ethenodeoxyadenosine, 3,N4-ethenodeoxycytidine and 7-N-(2-oxoethyl)guanine (the product of hydrolysis of 7-N-(2-oxoethyl)-deoxyguanosine). By contrast, when rats were exposed to [1,2-14C]vinyl chloride and when the liver DNA of these rats was subjected to similar procedures, no radioactive 'etheno' derivatives could be detected, but a radioactive peak was eluted with 7-N-(2-oxoethyl)guanine. This peak could be transformed into 7-N-(2-hydroxyethyl)guanine; the chromatographic behaviour of which was identical to the reference compound used by Ostermann-Golkar et al. (Biochem. biophys. Res. Commun., 76 (1977) 259). Thus, it is concluded that the compound described by these authors, 7-N-(2-oxoethyl)guanine is in fact the major product of base alkylation in DNA after exposure to vinyl chloride.
D000478:Alkylation; D000818:Animals; D004247:DNA / Q000378:metabolism*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014752:Vinyl Chloride / Q000378:metabolism*; D014753:Vinyl Compounds / Q000378:metabolism*
D003839:Deoxyadenosines; D014753:Vinyl Compounds; D003841:Deoxycytidine; D006147:Guanine; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine; C032220:7-N-(2-oxoethyl)guanine; D004247:DNA; D014752:Vinyl Chloride