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.