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首页> 外文期刊>Toxicology: An International Journal Concerned with the Effects of Chemicals on Living Systems >Polycyclic aromatic hydrocarbons in binary mixtures modulate the efficiency of benzo(a)pyrene to form DNA adducts in human cells.
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Polycyclic aromatic hydrocarbons in binary mixtures modulate the efficiency of benzo(a)pyrene to form DNA adducts in human cells.

机译：二元混合物中的多环芳香烃可调节苯并（a）re在人细胞中形成DNA加合物的效率。

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Exposure to polycyclic aromatic hydrocarbons (PAHs) always involves complex mixtures that may induce synergistic or antagonistic effects on the genotoxic properties and make risk assessment more difficult. In this study, we evaluated how particulate PAHs modulated the formation of DNA damage induced by carcinogenic benzo[a]pyrene (B[a]P). Single strand breaks and alkali labile sites, as well as BPDE-N(2)-dGuo DNA adducts were measured in the competent HepG2 cells by Comet assay and HPLC-tandem mass spectrometry, respectively. B[a]P, alone or in binary mixture with other PAHs (1 muM each), led to low amounts of strand breaks. In contrast, formation of BPDE-N(2)-dGuo adducts was significant and found to be enhanced in HepG2 co-treated for 14 h by B[a]P in the presence of either benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DB[a,h]A) or indeno[1,2,3-cd]pyrene (IP). Opposite results were obtained with benzo[k]fluoranthene (B[k]F). The same observations were made when cells were pre-incubated with PAH before incubation with B[a]P. These results show that the interactions between PAHs are not direct competition reactions. Emphasis was then placed on the modulation of B[a]P-induced DNA damage by B[b]F and B[k]F. No difference in the time-course formation of DNA damage was observed. However, dose-response relationship differed between these two PAHs with a concentration-dependent inhibition of BPDE-N(2)-dGuo DNA by B[k]F whereas a constant level of potentiation for B[b]F was observed for concentrations higher than 1 muM. Altogether, these results show that the genotoxicity of B[a]P in binary mixtures with other carcinogenic PAH may be modulated. In such cases, a potentiation of BPDE-N(2)-dGuo adduct formation is most often observed with exception of B[k]F. Several biological mechanisms may account for these observations, including binding of PAHs to the Ah receptor (AhR), their affinity toward CYP450 and competition for metabolism. These different interactions have to be considered when addressing the intricate issue of the toxicity of mixtures.
机译：暴露于多环芳烃（PAH）总是涉及复杂的混合物，这些混合物可能对基因毒性产生协同或拮抗作用，并使风险评估更加困难。在这项研究中，我们评估了颗粒状PAHs如何调节致癌性苯并[a] py（B [a] P）诱导的DNA损伤的形成。单链断裂和碱不稳定位点，以及BPDE-N（2）-dGuo DNA加合物分别通过彗星试验和HPLC串联质谱法在感受态的HepG2细胞中进行测量。 B [a] P单独使用或与其他PAHs（每个1μM）二元混合使用，可导致少量的链断裂。相比之下，BPDE-N（2）-dGuo加合物的形成是显着的，并且在苯并[b]荧蒽（B [b] F），二苯并[a，h]蒽（DB [a，h] A）或茚并[1,2,3-cd] py（IP）。用苯并[k]荧蒽（B [k] F）获得了相反的结果。在将细胞与B [a] P进行孵育之前，先将其与PAH进行预孵育时，会得到相同的观察结果。这些结果表明，多环芳烃之间的相互作用不是直接竞争反应。然后重点放在通过B [b] F和B [k] F调节B [a] P诱导的DNA损伤上。在DNA损伤的时间过程形成中没有观察到差异。但是，这两种PAH之间的剂量反应关系有所不同，B [k] F对BPDE-N（2）-dGuo DNA的浓度依赖性抑制，而B [b] F的恒定增高水平则观察到较高的浓度。大于1毫米。总之，这些结果表明，B [a] P在与其他致癌PAH的二元混合物中的遗传毒性可能得到了调节。在这种情况下，除B [k] F外，最常观察到BPDE-N（2）-dGuo加合物形成的增强作用。几种生物学机制可能解释了这些观察结果，包括PAH与Ah受体（AhR）的结合，它们对CYP450的亲和力和代谢竞争。解决混合物毒性的复杂问题时，必须考虑这些不同的相互作用。

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