title: 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.
abstract: 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.
authors.affiliation: Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: de Serres
authors.forename: H E
authors.initials: HE
authors.lastname: Brockman
mesh_terms: D000225:Adenine; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects; D004271:DNA, Fungal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005027:Ethylene Oxide / Q000633:toxicity*; D017353:Gene Deletion; D005800:Genes, Fungal / Q000187:drug effects*; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009152:Mutagenicity Tests; D009153:Mutagens / Q000145:classification / Q000633:toxicity; D009492:Neurospora crassa / Q000187:drug effects* / Q000235:genetics; D016273:Occupational Exposure; D017354:Point Mutation
chemical_list: D000395:Air Pollutants, Occupational; D004271:DNA, Fungal; D009153:Mutagens; D000225:Adenine; D005027:Ethylene Oxide