Cutaneous exposure to carcinogenic polycyclic aromatic hydrocarbons (PAH) occurs frequently in the industrialized workplace. In the present study, we addressed this topic in a series of experiments using human skin explants and organic extracts of relevant industrial products. PAH mixtures were applied topically in volumes containing either 10 or 1 nmol B[a]P. We first observed that although mixtures were very efficient at inducing expression of CYP450 1A1, 1A2, and 1B1, formation of adducts of PAH metabolites to DNA, like those of benzo[a]pyrene diol epoxide (BPDE), was drastically reduced as the complexity of the surrounding matrix increased. Interestingly, observation of a nonlinear, dose-dependent response with the least complex mixture suggested the existence of a threshold for this inhibitory effect. We then investigated the impact of simulated sunlight (SSL) on the effects of PAH in skin. SSL was found to decrease the expression of CYP450 genes when applied either after or more efficiently before PAH treatment. Accordingly, the level of DNA-BPDE adducts was reduced in skin samples exposed to both PAH and SSL. The main conclusion of our work is that both increasing chemical complexity of the mixtures and co-exposure to UV radiation decreased the production of adducts between DNA and PAH metabolites. Such results must be taken into account in risk management.

中文翻译：

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人皮肤外植体中多环芳烃的代谢和遗传毒性：混合效应和阳光调节。

在工业化的工作场所中经常发生皮肤接触致癌的多环芳烃（PAH）。在本研究中，我们通过使用人类皮肤外植体和相关工业产品的有机提取物的一系列实验解决了这一问题。将PAH混合物以10或1 nmol B [a] P的体积局部施用。我们首先观察到，尽管混合物在诱导CYP450 1A1、1A2和1B1的表达方面非常有效，但由于复杂性的原因，PAH代谢产物与DNA的加合物的形成（如苯并[a] re二醇环氧化合物（BPDE）的形成）大大减少了。周围矩阵的数量增加。有趣的是，用最不复杂的混合物观察到非线性，剂量依赖性反应表明存在抑制作用的阈值。然后，我们研究了模拟阳光（SSL）对PAH在皮肤中的影响。发现在PAH处理后或在PAH处理之前更有效地应用时，SSL会降低CYP450基因的表达。因此，暴露于PAH和SSL的皮肤样品中DNA-BPDE加合物的水平降低。我们工作的主要结论是，增加混合物的化学复杂性以及共同暴露于紫外线辐射都会降低DNA与PAH代谢物之间加合物的产生。在风险管理中必须考虑这些结果。我们工作的主要结论是，增加混合物的化学复杂性和共同暴露于紫外线辐射都会降低DNA与PAH代谢物之间加合物的产生。在风险管理中必须考虑这些结果。我们工作的主要结论是，增加混合物的化学复杂性以及共同暴露于紫外线辐射都会降低DNA与PAH代谢物之间加合物的产生。在风险管理中必须考虑这些结果。