Mutagenic potential of DNA adducts formed by diol-epoxides, triol-epoxides and the K-region epoxide of chrysene in mammalian cells.
The syn- and anti-isomers of chrysene-1,2-diol-3,4-oxide (syn-diol-epoxide and anti-diol-epoxide) and of 9-hydroxychrysene-1,2-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-diol-epoxide. The anti-diol-epoxide was approximately 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-1,2-diol-3,4-oxide appears to increase its chemical reactivity.
D002460:Cell Line; D002911:Chrysenes / Q000378:metabolism* / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D009153:Mutagens; D009690:Nucleic Acid Conformation; D010616:Phenanthrenes / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002911:Chrysenes; D009153:Mutagens; D010616:Phenanthrenes; C050404:9-hydroxychrysene-1,2-diol-3,4-oxide; C050403:chrysene-5,6-oxide; C021977:chrysene,2-diol-3,4-epoxide-1; D004247:DNA