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首页> 外文期刊>Archives of Toxicology >Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells
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Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells

机译：苯抑制诱导肿瘤抑制基因TP53突变模式的功能分析，功能分析是酵母分离的等位基因在人肺细胞中的功能分析

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Recent concern has centred on the effects of continuous exposure to low concentrations of benzene, both occupationally and environmentally. Although benzene has for a long time been recognised as a carcinogen for humans, its mechanistic pathway remains unclear. Since mutations in the tumour suppressor gene TP53 are the most common genetic alterations involved in human cancer, our objective was to establish the first mutational pattern induced by benzene on the TP53 gene in human type II-like alveolar epithelial A549 cells by using the Functional Analysis of Separated Alleles in Yeast (FASAY). Seventeen mutations linked to benzene exposure were found: 3 one- or two-base deletions, and 14 single nucleotide substitutions (1 nonsense and 13 missense mutations). A>G and G>A transitions were the most prevalent (23.5% for both). Other mutations included A>C transversions and deletions (3/17, 17.6% for both), G>T transversions (2/17, 11.8%) and A>T transversions (1/17, 5.9%). Data arising from this benzene-induced mutational pattern affecting TP53, a critical target gene in human carcinogenesis, have been compared with those reported in human acute myeloid leukaemia, the aetiology of which is clearly linked to benzene exposure, and in experimental benzene-induced carcinoma. This comparison suggests that A>G transition could be a fingerprint of benzene exposure in tumours. Furthermore, our results demonstrate that FASAY is a promising tool for the study of the carcinogenic potency of benzene in the human lung. Keywords A549 cells - Benzene - FASAY - Lung - Mutagenesis - TP53
机译：最近的关注集中在在职业和环境上持续暴露于低浓度苯中的影响。尽管长期以来人们一直认为苯是人类的致癌物，但其机理仍不清楚。由于抑癌基因TP53的突变是人类癌症中最常见的遗传变异，因此我们的目标是通过功能分析来建立苯诱导的人类II型肺泡上皮A549细胞中TP53基因的第一个突变模式。酵母中分离的等位基因的表达（FASAY）。发现了17个与苯暴露有关的突变：3个一或两个碱基的缺失，以及14个单核苷酸取代（1个无意义的突变和13个错义的突变）。 A> G和G> A过渡最为普遍（两者均占23.5％）。其他突变包括A> C转化和缺失（3/17，均为两者的17.6％），G> T转化（2 / 17，11.8％）和A> T转化（1 / 17，5.9％）。已将这种影响人致癌作用的关键靶基因TP53的苯诱导突变模式产生的数据与人类急性髓细胞白血病的病因明确与苯暴露以及实验性苯诱导的癌症相关的报道进行了比较。 。该比较表明，A> G过渡可能是肿瘤中苯暴露的指纹。此外，我们的结果表明，FASAY是研究人肺中苯致癌潜能的有前途的工具。关键词A549细胞-苯-FASAY-肺-诱变-TP53

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