HAMSTER LEYDIG-CELLS ARE LESS SENSITIVE TO ETHANE DIMETHANESULFONATE WHEN COMPARED TO RAT LEYDIG-CELLS BOTH IN-VIVO AND IN-VITRO

It has been reported that ethane dimethanesulfonate (EDS) is a Leydig cell toxicant that affects rats and hamsters (Kerr et al., 1987), while, in contrast, the Leydig cells of mice are relatively insensitive to the toxicant. In the rat, there is a rapid decline in levels of testosterone (T) within hours after EDS administration. However, T production, spermiogenesis, and fertility are restored within a few weeks as new Leydig cells are formed from undifferentiated cells in the interstitium of the testis. In an earlier study, we found, as expected, that ejaculated sperm counts (ESCs) reached a nadir 10 days after adult rats were dosed with EDS at 65 mg/kg ip along with serum and testicular T, testis and seminal vesicle weights, and in vitro T production, while, in contrast, EDS at 65 mg/kg had no effect on these endpoints in the Syrian hamster (Gray et al., 1992). In the current study, when EDS was administered to 6, 12, and 18 month old hamsters at 100 mg/kg, it produced subtle effects on serum T and sex accessory gland weights, while dramatic effects were seen in similarly exposed rats. In addition, when testes were examined by light microscopy all treated rats displayed severely reduced Leydig cell numbers, while, in contrast, only one-third of the EDS-treated hamsters were affected, having moderately reduced Leydig cell numbers. In support of the histological data, 3 beta-HSD enzyme activity was reduced by 99% of control in EDS-treated rats, but it was reduced by only 35% of control in EDS-treated hamsters. An in vitro analysis of the effects of EDS on LH-stimulated T production by quartered testes demonstrated that the hamster testis was less sensitive to the direct effects of EDS than the rat testis. The IC50 after 3 hr in culture was greater than 1800 mu g EDS/ml for the hamster quarter testes, while the IC50 for the rat quarter testes was 320 mu g EDS/ml. In summary, these results demonstrate in vivo and in vitro that Leydig cells of hamsters are less sensitive to EDS than those of the adult rat. (C) 1995 Academic Press, Inc.