Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Exp Dermatol. 2024 Mar;33(3):e15044. doi: 10.1111/exd.15044.
Polycyclic aromatic hydrocarbons with the key substance benzo[a]pyrene (B[a]P) are widespread pollutants in the environment and at working places. Nonetheless, the exact underlying mechanisms of toxicological effects caused by B[a]P especially in absence and presence of UV irradiation remain uncertain. This study examines variations in exposure conditions: low B[a]P (4 nM), low B[a]P + UV and high B[a]P (4 μM), selected based on pertinent cytotoxicity assessments. Following cell viability evaluations post-treatment with varied B[a]P concentrations and UV irradiation, the identified concentrations underwent detailed metabolomic analysis via gas chromatography-mass spectrometry. Subsequently, resulting changes in metabolic profiles across these distinct exposure groups are comprehensively compared. Chemometric analyses showed modest regulation of metabolites after low B[a]P exposure compared to control conditions. High B[a]P and low B[a]P + UV exposure significantly increased regulation of metabolic pathways, indicating that additional UV irradiation plus low B[a]P is as demanding for the cells as higher B[a]P treatment alone. Further analysis revealed exposure-dependent regulation of glutathione-important for oxidative defence-and purine metabolism-important for DNA base synthesis. Only after low B[a]P, oxidative defence appeared to be able to compensate for B[a]P-induced perturbations of the oxidative homeostasis. In contrast, purine metabolism already responded towards adversity at low B[a]P. The metabolomic results give an insight into the mechanisms leading to the toxic response and confirm the strong effects of co-exposure on oxidative defence and DNA repair in the model studied.
多环芳烃，其关键物质为苯并[a]芘（B[a]P），是环境和工作场所中广泛存在的污染物。然而，B[a]P 引起的毒理学效应的确切潜在机制，特别是在缺乏和存在紫外线照射的情况下，仍不确定。本研究考察了暴露条件的变化：基于相关细胞毒性评估，选择低 B[a]P（4 nM）、低 B[a]P+UV 和高 B[a]P（4 μM）。在用不同浓度 B[a]P 和紫外线照射处理后进行细胞活力评估，对鉴定出的浓度进行气相色谱-质谱法详细代谢组学分析。随后，全面比较这些不同暴露组中代谢谱的变化。化学计量学分析表明，与对照条件相比，低 B[a]P 暴露后代谢物的调节程度适中。高 B[a]P 和低 B[a]P+UV 暴露显著增加了代谢途径的调节，表明额外的 UV 照射加上低 B[a]P 对细胞的要求与单独高 B[a]P 处理一样高。进一步的分析表明，B[a]P 依赖性调节谷胱甘肽——对氧化防御很重要——和嘌呤代谢——对 DNA 碱基合成很重要。只有在低 B[a]P 暴露后，氧化防御似乎才能补偿 B[a]P 引起的氧化平衡紊乱。相比之下，嘌呤代谢在低 B[a]P 时已经对逆境做出了反应。代谢组学结果深入了解了导致毒性反应的机制，并证实了共同暴露对所研究模型中的氧化防御和 DNA 修复的强烈影响。
