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, and 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, N 6- ethenodeoxyadenosine, 3, N 4- 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.