de Serres F J, Brockman H E
Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Mutat Res. 1995 Apr;328(1):31-47. doi: 10.1016/0027-5107(94)00194-a.
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 chemical mutagens 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.
环氧乙烷（ETO）是一种重要的工业中间体，广泛用于生产乙二醇、作为熏蒸剂以及作为各种医疗器械的首选消毒剂。研究了环氧乙烷在粗糙脉孢菌双组分异核体（H-12）的腺嘌呤-3（ad-3）区域诱导特定基因座突变的致突变性。这些用环氧乙烷进行的研究目的是对其致突变效力进行排名，并将其诱导特定基因座突变的突变谱与这种低等真核生物中的其他化学诱变剂进行比较。异核体H12的ad-3区域的特定基因座突变是由紧密连锁的ad-3A和ad-3B基因座的基因/点突变、多位点缺失突变和多基因座突变引起的。这些主要的基因型类别与在高等生物中可以检测到的特定基因座突变类型相似。将H-12的分生孢子悬浮液用五种不同浓度的环氧乙烷（0.1 - 0.35%）在25℃下处理3小时。使用对照和经环氧乙烷处理的分生孢子悬浮液，通过基于色素积累而非对腺嘌呤需求的非选择性方法，获得失活的剂量反应曲线以及ad-3正向突变的总体诱导情况。这些实验的结果是：（1）环氧乙烷诱导的ad-3区域特定基因座突变的剂量反应曲线斜率为1.49±0.07，（2）最大正向突变频率在每10^6个存活者中有10至100个ad-3突变之间；因此，环氧乙烷是一种中度诱变剂。使用经典遗传学测试来表征两种处理（0.25%和0.35%）中每种处理诱导的环氧乙烷ad-3突变。总体数据库表明，环氧乙烷诱导的ad-3突变中，96.9%是由ad-3A和ad-3B基因座的基因/点突变引起的，以及3.1%是由多位点缺失突变引起的。在脉孢菌的ad-3正向突变试验中，将环氧乙烷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。讨论了其他人对脉孢菌关于环氧乙烷的特定基因座数据以及在小鼠和果蝇实验中的数据的利用情况，用于评估人类在工作场所接触环氧乙烷导致的生殖细胞效应的遗传风险。
