Detection of N2,3-ethanoguanine in DNA after treatment with chloroacetaldehyde in vitro.

The reaction of chloroacetaldehyde, a reactive metabolic of the carcinogen vinyl chloride, with DNA produces in addition to the hitherto known adducts, 1,N6-ethenoadenine and 3,N4-ethenocytosine, an ethenoguanine adduct, namely N2,3-ethenoguanine. This adduct is formed in the reaction of chloroacetaldehyde with the free base as well. After DNA hydrolysis followed by isolation of this new adduct by h.p.l.c., its mass spectrum and fluorescence spectrum are identical with those published in the literature for the chemically synthesized N2,3-ethenoguanine. The formation of only this guanine derivative out of several theoretically possible reaction products allows the formulation of a reaction scheme. The absence of 7-(2-oxoethyl)-guanine, another recently detected DNa adduct of vinyl chloride, in chloroacetaldehyde-treated DNA suggests its origin from the other reactive metabolic of vinyl chloride, chloroethylene oxide. The potential of N2,3-ethenoguanine to lead to misincorporation of deoxythymidine monophosphate opposite of guanine and the high fluorescence of this adduct provide it with potentially high biological significance and ease of analytical monitoring.