title: Ethylene oxide inhalation at different exposure-rates affects binding levels in mouse germ cells and hemoglobin. Possible explanation for the effect.
abstract: Male mice were exposed to [3H]EtO by inhalation at different exposure rates (300 parts per million (ppm) of EtO for 1 h: 150 ppm for 2 h: 75 ppm for 4 h). The total exposure was fixed at 300 ppm-h. The amount of EtO binding to developing spermatogenic stages, to sperm DNA, to testis DNA and to hemoglobin was then measured as a function of the EtO exposure rate. Generally, as the exposure rate increased there was an increase in the amount of EtO binding to the targets. For example, alkylation of sperm from the caudal epididymides 6 d posttreatment, of DNA from the vas sperm (averaged over 4 time points), of testis DNA (90 min posttreatment), and of hemoglobin (averaged over 4 time points), was 2.0 +/- 0.2 (SD), 1.8 +/- 0.4, 2.9 +/- 0.3, and 1.5 +/- 0.1 times greater, respectively, after an exposure to 300 ppm for 1 h than after an exposure to 75 ppm for 4 h. The testicular DNA from animals exposed to 300 ppm of [3H]EtO for 1 h was also analyzed for the presence of N7-hydroxyethylguanine (N7HEG) and O6-hydroxyethylguanine (O6HEG). The half-life (T1 2) of the N7HEG in the testis DNA was calculated to be 2.8 d. This lesion was removed relatively rapidly from the testis DNA and was probably excised by enzymatic repair. No formation of O6HEG was detected in any of the testis DNA samples analyzed. Additional experiments showed that the exposure rate effect was the result of less total EtO being taken in by the mice over long exposure times compared to that taken in during shorter exposure times at higher concentrations. This result argues against the idea that the exposure rate effect is the result of physiological/enzymological changes affecting transport or metabolism of the chemical within the animals under different exposure rate conditions.
authors.affiliation: Biology Division, Oak Ridge National Laboratory, TN 37831-8077.
authors.forename: G A
authors.initials: GA
authors.lastname: Sega
authors.forename: P A
authors.initials: PA
authors.lastname: Brimer
authors.forename: E E
authors.initials: EE
authors.lastname: Generoso
mesh_terms: D000280:Administration, Inhalation; D000478:Alkylation; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D005027:Ethylene Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D051379:Mice; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
chemical_list: D006454:Hemoglobins; C035018:N(7)-hydroxyethylguanine; D006147:Guanine; D004247:DNA; D005027:Ethylene Oxide