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Lack of Miscoding Properties of 7-(2-Oxoethyl)guanine, the Major Vinyl Chloride-DNA Adduct

International Agency for Research on Cancer, Division of Environmental Carcinogenesis, 150 Cours Albert Thomas, F 69372, Lyon Cedex 08, France [A. B., H. B], and Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystrasse 67, D 4600 Dortmund, Federal Republic of Germany [R. J. L.]

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 (>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.

¹ Part of this work was performed under an IARC Research Training Fellowship at the International Agency for Research on Cancer, Lyon, France.

² To whom requests for reprints should be addressed.

Received 12/13/83. Revised 8/14/84. Revised 12/11/84. Accepted 2/21/85.

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