Roles of etheno-DNA adducts in tumorigenicity of olefins.

Cyclic DNA adducts bearing an "etheno" structure have been described to occur after interaction with metabolites of halogenated olefins. Extensive work has been published on adducts of vinyl chloride, both in vitro and in vivo. The major DNA adduct of vinyl chloride is 7-(2-oxoethyl)guanine, but an important minor adduct appears to be N2,3-ethenoguanine. Other etheno adducts, i.e., 1, N6-ethenoadenine and 3, N4-ethenocytosine, are readily formed with DNA, vinyl chloride, and a metabolizing system in vitro and with RNA in vivo, but usually are not detected as DNA adducts in vivo. Other compounds that have been studied with respect to possible formation of etheno DNA adducts are vinyl bromide (which is more or less completely analogous to vinyl chloride), acrylonitrile, vinyl acetate and vinyl carbamate. Proposals of possible structures of DNA adducts with an etheno structure have been promutagenic potential of these lesions which may lead to misincorporation of wrong DNA bases in newly synthesized DNA.