Germ-cell mutagenesis and GSH depression in reproductive tissue of the F-344 rat induced by ethyl methanesulfonate.
Sensitivity of male F-344 rats to the dominant lethal (DL) mutagenic effect of ethyl methanesulfonate (EMS) was studied in conjunction with an evaluation of EMS-induced depression of glutathione (GSH) in testis, epididymis and vas deferens. At the maximal effect, during week 3 (days 15-19 post-EMS), a dosage of 50 mg/kg caused 13.3% fetal death (FD) vs. 3.3% in controls, while 100 mg/kg caused 56.6% FD in the same interval. EMS maximally depressed GSH to 33%, 54% and 77% of control in vas, epididymis and testis respectively. The slope of the DL dose-response curve for EMS in rats shows a 3-4-fold greater sensitivity than that reported for mice. The steepness of this curve suggests that small perturbations in endogenous protective mechanisms, such as GSH depression, may exert a greater proportional effect on germ-cell mutagenesis in rats which should be more readily observable than in mice. EMS and other electrophilic toxicants may thus influence their own primary reproductive toxicity and/or that of other agents by depression of GSH in male reproductive tissue.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005799:Genes, Dominant; D005804:Genes, Lethal; D005837:Genitalia, Male / Q000032:analysis / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013091:Spermatogenesis / Q000187:drug effects*
D005020:Ethyl Methanesulfonate; D005978:Glutathione