Phillips D H, Glatt H R, Seidel A, Bochnitschek W, Oesch F, Grover P L
Carcinogenesis. 1986 Oct;7(10):1739-43. doi: 10.1093/carcin/7.10.1739.
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.
对1,2 - 二羟基 - 3,4 - 氧化屈的顺式和反式异构体（顺式二醇环氧化物和反式二醇环氧化物）、9 - 羟基 - 1,2 - 二羟基 - 3,4 - 氧化屈（顺式三醇环氧化物和反式三醇环氧化物）以及K区环氧化物屈 - 5,6 - 氧化物进行了测试，以检测它们在V79中国仓鼠细胞中诱导6 - 硫鸟嘌呤抗性突变体的能力。通过³²P后标记分析确定了每种化合物在V79细胞中形成的DNA加合物水平。就每nmol化合物给药后的突变频率而言，最有效的诱变剂是反式三醇环氧化物，其活性是反式二醇环氧化物的1.7倍。反式二醇环氧化物的活性比顺式三醇环氧化物和顺式二醇环氧化物大约高10倍，而顺式三醇环氧化物和顺式二醇环氧化物的活性又比K区环氧化物高几倍。然而，当结果以每pmol形成的总加合物的突变数表示时，反式三醇环氧化物和反式二醇环氧化物显示出相似的效力，并且活性约为其他三种化合物的两倍。因此，顺式和反式异构体与DNA形成的加合物构象差异可能是它们诱变潜力不同的原因；在1,2 - 二羟基 - 3,4 - 氧化屈的9位存在酚羟基似乎会增加其化学反应性。
