Dominant visible and electrophoretically expressed mutations induced in male mice exposed to ethylene oxide by inhalation

Abstract

The offspring of DBA/2J male mice exposed to ethylene oxide (EtO) by inhalation had an increased incidence of both dominant visible and electrophoretically detected mutations over that found in control populations. The progeny at risk were obtained from matings during the exposure period and were the products of germ cells that were exposed throughout the entire spermatogenic process. The results reported here suggest that male germ cells repeatedly exposed to EtO during spermatogenesis are susceptible to EtO-induced transmissible damage.

N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome.

“…Blood and kidney samples from the (C57BL/6J x DBA/2J)F1 progeny were screened for variations at 32 loci by starch gel electrophoresis and broad-range isoelectric focusing, as described elsewhere (18,19). CA II in F1 animals appears as two bands (i.e., CA Ila and CA Ilb) on the broad-range focusing gels.…”

“…Intercrosses of carriers and additional backcrosses were also performed. The CA II phenotypes of all progeny were determined in blood samples by broad-range isoelectric focusing (19) or by electrophoresis on cellulose acetate (Cellogel, Whatman) at pH 5.4. Developmental curves were generated by weighing the mice several times a week.…”

Testicular Damage Caused by Inhalation of Ethylene Oxide in Rats: Light and Electron Microscopic Studies

“…Any test for evaluating the subchronic effects of an agent on spermatogenesis needs to be extended over 6 cycles of the seminiferous epithelium in order to allow examination of all exposed germ cells (1 (32). However, the mutagenic effects of EtO exposure were found only in mature spermatozoa and late spermatids (13,16,21,22 (33), exposure to 2,4-dinitrotoluene (4), 2,5-hexanedione (5), n-hexane (14), cytochalasin D (48), DL-6-(N-2-pipecolinomethyl)-5-hydroxy-indane (17), methylxanthines (20), cyclohexylamine (12), methyl chloride (6), massive doses of Vitamin B6 (29), cryptorchidism (28), ligation of the ductuli efferentes (3), and vasectomy (19).…”

“…The mutagenicity of EtO on mammalian germ cell lines has been proven by studying its prenatal dominant lethal effects in both mice (13,21,22) and rats (16), and the increase in heritable translocations and dominant visible and electrophoretically expressed mutations in mice (32). A decrease in the fertility index of male rats (16) and both male and female rats (52) following exposure to EtO has been reported.…”

Approaches to assessing genetic risks from exposure to chemicals.

“…In mice, heritable translocations induced by chemical mutagens are sometimes associated with neurological disorders, blindness, and skeletal abnormalities (26,27). In humans, cases are known where translocations are associated with skeletal abnormalities and various other conditions.…”