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
Fj. Deserres et He. Brockman, 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, Mutation research, 328(1), 1995, pp. 31-47
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.