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首页> 外文期刊>Mutation Research: International Journal on Mutagenesis, Chromosome Breakage and Related Subjects >Ethylene oxide: induction of specific-locus mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa and implications for genetic risk assessment of human exposure in the workplace.
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Ethylene oxide: induction of specific-locus mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa and implications for genetic risk assessment of human exposure in the workplace.

机译:环氧乙烷:诱导神经孢菌异核体12的ad-3区域中特定位点的突变,以及对工作场所中人类暴露的遗传风险评估的意义。

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Ethylene oxide (ETO) is an important industrial intermediate used extensively in the production of ethylene glycol, as a fumigant, and as a sterilant of choice for various medical devices. The mutagenicity of ETO was studied for the induction of specific-locus mutations in the adenine-3 (ad-3) region of a two-component heterokaryon (H-12) of Neurospora crassa. The objectives of these studies with ETO were to rank its mutagenic potency and to compare its mutational spectrum for induced specific-locus mutations with other chemical mutagens in this lower eukaryotic organism. Specific-locus mutations in the ad-3 region of heterokaryon H12 result from gene/point mutations at the closely linked ad-3A and ad-3B loci, multilocus deletion mutations and multiple-locus mutations. These major genotypic classes are similar to the types of specific-locus mutations that can be detected in higher organisms. Conidial suspensions of H-12 were treated with five different concentrations of ETO (0.1-0.35%) for 3 h at 25 degrees C. Control and ETO-treated conidial suspensions were used to obtain dose-response curves for inactivation as well as the overall induction of ad-3 forward mutations using a non-selective method based on pigment accumulation rather than a requirement for adenine. The results from these experiments are: (1) the slope of the dose-response curve for ETO-induced specific-locus mutations in the ad-3 region is 1.49 +/- 0.07, and (2) the maximum forward-mutation frequency fell between 10 and 100 ad-3 mutations per 10(6) survivors; therefore, ETO is a moderate mutagen. Classical genetic tests were used to characterize the ETO-induced ad-3 mutations from each of two treatments (0.25 and 0.35%). The overall data base demonstrates that ETO-induced ad-3 mutations result from a high percentage (96.9%) of gene/point mutations at the ad-3A and ad-3B loci, as well as from a low percentage (3.1%) of multilocus deletion mutations. The mutagenic activity of ETO is compared with the mutagenic specificity of other chemicalmutagens and carcinogens in the ad-3 forward-mutation assay in Neurospora. The utilization of the Neurospora specific-locus data on ETO and those from experiments in the mouse and Drosophila, by others, is discussed for genetic risk assessment of germ-cell effects resulting from human exposure to ETO in the workplace.
机译:环氧乙烷(ETO)是重要的工业中间体,广泛用于生产乙二醇,作为熏蒸剂和作为各种医疗设备的首选灭菌剂。研究了ETO的诱变性,以诱导神经孢菌两组分异核体(H-12)的腺嘌呤3(ad-3)区域中的特定基因座突变。这些用ETO进行研究的目的是对这种较低的真核生物的诱变能力进行分级,并比较其诱变的特异性位点突变与其他化学诱变剂的突变谱。杂核H12的ad-3区域中的特定基因座突变是由紧密连锁的ad-3A和ad-3B位点的基因/点突变,多基因座缺失突变和多基因座突变引起的。这些主要的基因型类别类似于可以在高等生物中检测到的特定基因座突变的类型。将H-12的分生孢子悬浮液在25摄氏度下用五种不同浓度的ETO(0.1-0.35%)处理3小时。对照和经ETO处理的分生孢子悬浮液用于获得灭活的剂量反应曲线以及总体使用基于色素积累而不是腺嘌呤的非选择性方法诱导ad-3正向突变。这些实验的结果是:(1)ETO诱导的ad-3区域中特定位点突变的剂量反应曲线的斜率为1.49 +/- 0.07,以及(2)最大正向突变频率下降每10(6)个幸存者有10至100个ad-3突变;因此,ETO是中等诱变剂。经典的遗传学测试用于表征两种治疗方法(0.25和0.35%)中ETO诱导的ad-3突变。总体数据库表明,ETO诱导的ad-3突变是由ad-3A和ad-3B位点的基因/点突变的高百分比(96.9%)以及低百分比(3.1%)的基因/点突变引起的多位点缺失突变。在Neurospora中的ad-3正向突变测定中,将ETO的诱变活性与其他化学诱变剂和致癌物的诱变特异性进行了比较。讨论了利用ETO上的Neurospora特定位点数据以及其他人在小鼠和果蝇中进行的实验,对人类在工作场所中暴露于ETO引起的生殖细胞效应进行遗传风险评估。

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