Vulpe Laboratory, Graduate Group in Environmental Health Sciences, University of California Berkeley, CA, USA.
Front Genet. 2013 Feb 8;3:316. doi: 10.3389/fgene.2012.00316. eCollection 2012.
Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems.
苯并[a]芘（BaP）是一种普遍存在、强效且完全的致癌物质，源于不完全的有机燃烧。BaP 可以形成 DNA 加合物，但其他机制可能在毒性中起作用。我们在酿酒酵母中使用功能毒理学方法来评估细胞对 BaP 抗性的遗传要求。此外，我们还检查了参与各种应激反应途径的关键基因的翻译活性。我们在酵母中确定了多个参与调节 BaP 毒性的基因和过程，这支持 DNA 损伤作为毒性的主要机制，但也确定了其他潜在的毒性途径。基因本体富集分析表明，DNA 损伤和修复以及氧化还原稳态和氧化应激是细胞对 BaP 反应的关键过程，这表明 BaP 在酵母和哺乳动物中的作用模式相似。有趣的是，有毒物质的外排也被认为是细胞敏感性的一个潜在的新调节因子。特别是，我们鉴定了几个具有人类同源物（溶质载体家族 22）的转运体，它们可能在哺乳动物系统中发挥作用。
