Mutagenic potential of DNA adducts formed by diol-epoxides, triol-epoxides and the K-region epoxide of chrysene in mammalian cells

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Abstract
The syn- and anti-tsomers of chrysene-l,2-diol-3,4oxide (syn-diol-epoxide and anti-diol-epoxide) and of 9-hydroxychry-sene-l, 2-diol-3, 4-oxide (syn-triol-epoxide and anti-triol-epoxide) and chrysene-5,6-oxide, the K-region epoxide, were tested for their ability to induce 6-thioguanine-resistant mutants in V79 Chinese hamster cells. The levels of DNA adducts formed by each compound in the V79 cells were determined by 32P-post-labelling analysis. The most potent mutagen, in terms of the mutation frequency/nmol compound administered, was the anti-triol-epoxide, which was 1.7 times as active as the anti-triol-epoxide. The anti-diol-epoxide was ∼10 times more active than both the syn-triol-epoxide and the syn-diol-epoxide, which in turn were several times more active than the K-region epoxide. However, when the results were expressed as mutations/pmol total adducts formed, the anti-triol-epoxide and anti-diol-epoxide were shown to be of similar potency and approximately twice as active as the other three compounds. Thus differences in the conformation of adducts formed with DNA by syn- and anti-isomers may be responsible for their different mutagenic potentials; the presence of a phenolic OH-group at the 9-position of a chrysene-l,2-diol-3,4-oxide appears to increase its chemical reactivity.