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

Ethylene oxide (ETO) is an important industrial intermediate used exte nsively in the production of ethylene glycol, as a fumigant, and as a sterilant of choice for various medical devices. The mutagenicity of E TO was studied for the induction of specific-locus mutations in the ad enine-3 (ad-3) region of a two-component heterokaryon (H-12) of Neuros pora 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 eu karyotic organism. Specific-locus mutations in the ad-3 region of hete rokaryon H-12 result from gene/point mutations at the closely linked a d-M and ad-3B loci, multilocus deletion mutations and multiple-locus m utations. These major genotypic classes are similar to the types of sp ecific-locus mutations that can be detected in higher organisms. Conid ial suspensions of H-12 were treated with five different concentration s 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 inac tivation as well as the overall induction of ad-3 forward mutations us ing 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 ETC-induced specific-locus mu tations 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) s urvivors; therefore, ETO is a moderate mutagen. Classical genetic test s were used to characterize the ETO-induced ad-3 mutations from each o f two treatments (0.25 and 0.35%). The overall data base demonstrates that ETC-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 c hemical 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 far genetic risk assessment of germ-cell effects resulti ng from human exposure to ETO in the workplace.