Lack of miscoding properties of 7-(2-oxoethyl)guanine, the major vinyl chloride-DNA adduct.
Chloroethylene oxide, an ultimate carcinogenic metabolite of vinyl chloride, was reacted with poly(deoxyguanylate-deoxycytidylate); the nucleic acid base adducts, 7-(2-oxoethyl)guanine and 3,N4-ethenocytosine, were analyzed by reverse-phase high-performance liquid chromatography. Chloroethylene oxide-modified poly(deoxyguanylate-deoxycytidylate) was assayed as template in a replication fidelity assay with Escherichia coli DNA polymerase I, and the newly synthesized product was subjected to nearest-neighbor analysis. Misincorporation rates of deoxyadenosine monophosphate and thymidine monophosphate were found to increase with the level of template modification. About 80% of the mispairing events were located opposite minor cytosine lesions. 7-(2-Oxoethyl)guanine, the major adduct identified (greater than 98% of the adducts), did not miscode for either thymine or adenine, failing to support an earlier hypothesis that the cyclic hemiacetal form, O6,7-(1'-hydroxyethano)guanine, could, by analogy with O6-methyl- and O6-ethylguanine, simulate adenine. Our results indicate that direct miscoding of 7-(2-oxoethyl)-guanine may contribute only slightly to the induction of mutations by chloroethylene oxide or vinyl chloride.
D002851:Chromatography, High Pressure Liquid; D004247:DNA; D004261:DNA Replication / Q000187:drug effects*; D003838:Deoxyadenine Nucleotides; D005027:Ethylene Oxide / Q000031:analogs & derivatives / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives*; D011089:Polydeoxyribonucleotides; D013938:Thymidine Monophosphate; D014752:Vinyl Chloride / Q000633:toxicity
D003838:Deoxyadenine Nucleotides; D011089:Polydeoxyribonucleotides; C019530:poly(dC-dG); D013938:Thymidine Monophosphate; D006147:Guanine; C012873:2'-deoxy-5'-adenosine monophosphate; C032220:7-N-(2-oxoethyl)guanine; C015061:chloroethylene oxide; D004247:DNA; D005027:Ethylene Oxide; D014752:Vinyl Chloride