UVA light-induced DNA cleavage by isomeric methylbenz[a]anthracenes
UVA light-induced DNA cleavage by isomeric methylbenz[a]anthracenes
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DOI：
10.1021/tx015567n
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发表时间：
2002-03-01
影响因子：
4.1
通讯作者：
Yu, H
中科院分区：
文献类型：
--
作者：
Dong, S;Fu, PP;Yu, H
本文研究了12种单甲基取代苯并[a]蒽（MBA）及其母体化合物苯并[a]蒽（BA）和致癌物7，12-二甲基苯并[a]蒽（DMBA）沿着对UVA光诱导的DNA单链断裂作用。根据14种化合物的相对DNA单链光切割效率，将它们分为三组：（1）强DNA切割剂，4-MBA、5-MBA、6-MBA、8-MBA、9-MBA、10-MBA和BA;（2）中等DNA切割剂，1-MBA、2-MBA、3-MBA和11-MBA;和（3）弱DNA切割剂，7-MBA、12-MBA和DMBA。相对DNA光切割效率与每个MBA的最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）之间的能隙非常好地平行，表明DNA切割与它们的激发态性质有关。BA的7位和12位是两个独特的位点。在7或12（或两者）位置的甲基取代降低HOMO-LUMO间隙并大大降低DNA光切割效率。UVA光诱导的光降解选定的MBA揭示，甲基取代在7或12（或两者）的位置大大提高了降解速率。7-MBA、12-MBA和DMBA的光降解产生的产物在介导DNA切割方面效率低得多。以5-MBA为例的其他MBA的光降解产生光氧化产物5-MBA-7，12-醌，其在光下相对稳定，并且是比5-MBA本身更强的DNA光切割剂。甲基取代在7或12位以外的MBA的DNA光切割效率更高，至少部分是由于7，12-醌的形成。几种MBA的光诱导DNA单链切割效率与其他研究小组观察到的光诱导毒性平行，表明MBA的光诱导DNA切割是光毒性的来源。由于一些多环芳烃如煤焦油在商业上被用作乳膏、治疗剂或软膏，或那些受到多环芳烃污染的屋顶工人和沥青工人，多环芳烃和光（皮肤中）的组合可能对人类造成更大的健康风险。
UVA light-induced DNA single strand cleavage by a set of 12 monomethyl substituted benz[a]anthracenes (MBAs) along with their parent compound, benz[a]anthracene (BA), and the potent carcinogen, 7,12-dimethylbenz [a] anthracene (DMBA), was studied. On the basis of the relative DNA single strand photocleavage efficiency of the fourteen compounds, they are divided into three groups: (1) strong DNA cleavers, 4-MBA, 5-MBA, 6-MBA, 8-MBA, 9-MBA, 10-MBA, and BA; (2) medium DNA cleavers, 1-MBA, 2-MBA, 3-MBA, and 11-MBA; and (3) weak DNA cleavers, 7-MBA, 12-MBA, and DMBA. The relative DNA photocleavage efficiency parallels very well with the energy gap between the highest-occupied-molecular-orbitaI (HOMO) and the lowest-unoccupied-molecular-orbitaI (LUMO) of each MBA, indicating that the DNA cleavage is related to their excited-state properties. The 7 and 12 positions of BA are two unique sites. Methyl substitution at either 7 or 12 (or both) positions lowers the HOMO-LUMO gap and greatly diminishes the DNA photocleavage efficiency. UVA light-induced photodegradation of selected MBAs reveals that methyl substitution at either 7 or 12 (or both) positions greatly enhances the degradation rate. Photodegradation of 7-MBA, 12-MBA, and DMBA yields products that are much less effective in mediating DNA cleavage. Photodegradation of other MBAs, exemplified by 5-MBA, yields a photooxidation product 5-MBA-7,12-quinone which is relatively stable under light and is a stronger DNA photocleaver than 5-MBA itself. The higher efficiency of DNA photocleavage for MBAs with methyl substitution at positions other than 7 or 12 is due, at least in part, to the formation of 7,12-quinone. Light-induced DNA single strand cleavage efficiency for several MBAs parallels the light-induced toxicity observed by other research groups, suggesting that light-induced DNA cleavage of MBAs are the source for phototoxicity. Since some PAHs such as coal tar are used commercially as creams, therapeutic agents, or ointments, or those roofers and asphalt workers that are subject to contamination with PAHs, the combination of PAHs and light (in the skin) may present a greater health risk to humans.