DNA damage is ubiquitous and can arise from endogenous or exogenous sources. DNA-damaging alkylating agents are present in environmental toxicants as well as in cancer chemotherapy drugs and are a constant threat, which can lead to mutations or cell death. All organisms have multiple DNA repair and DNA damage tolerance pathways to resist the potentially negative effects of exposure to alkylating agents. In bacteria, many of the genes in these pathways are regulated as part of the SOS reponse or the adaptive response. In this work, we probed the cellular responses to the alkylating agents chloroacetaldehyde (CAA), which is a metabolite of 1,2-dichloroethane used to produce polyvinyl chloride, and styrene oxide (SO), a major metabolite of styrene used in the production of polystyrene and other polymers. Vinyl chloride and styrene are produced on an industrial scale of billions of kilograms annually and thus have a high potential for environmental exposure. To identify stress response genes in E. coli that are responsible for tolerance to the reactive metabolites CAA and SO, we used libraries of transcriptional reporters and gene deletion strains. In response to both alkylating agents, genes associated with several different stress pathways were upregulated, including protein, membrane, and oxidative stress, as well as DNA damage. E. coli strains lacking genes involved in base excision repair and nucleotide excision repair were sensitive to SO, whereas strains lacking recA and the SOS gene ybfE were sensitive to both alkylating agents tested. This work indicates the varied systems involved in cellular responses to alkylating agents, and highlights the specific DNA repair genes involved in the responses.

中文翻译：

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大肠杆菌对烷基化剂氯乙醛和氧化苯乙烯的反应。

DNA损伤无处不在，可能源于内源或外源。破坏DNA的烷基化剂存在于环境有毒物质以及癌症化学疗法药物中，并且是持续不断的威胁，可能导致突变或细胞死亡。所有生物都有多种DNA修复和DNA损伤耐受途径，以抵抗暴露于烷基化剂的潜在负面影响。在细菌中，这些途径中的许多基因都作为SOS反应或适应性反应的一部分受到调控。在这项工作中，我们探究了对烷基化剂氯乙醛（CAA）（用于生产聚氯乙烯的1,2-二氯乙烷的代谢物）和苯乙烯氧化物（SO）（用于生产苯乙烯的主要代谢物）的细胞反应。聚苯乙烯和其他聚合物。氯乙烯和苯乙烯的工业规模每年生产数十亿公斤，因此具有很高的环境暴露潜力。为了确定大肠杆菌中对反应性代谢产物CAA和SO的耐受性负责的应激反应基因，我们使用了转录报告基因和基因缺失菌株的文库。响应于两种烷基化剂，与几种不同应激途径相关的基因被上调，包括蛋白质，膜和氧化应激以及DNA损伤。缺乏涉及碱基切除修复和核苷酸切除修复的基因的大肠杆菌菌株对SO敏感，而缺乏recA和SOS基因ybfE的菌株对两种测试的烷基化试剂敏感。这项工作表明细胞对烷基化剂的反应涉及多种系统，