Distribution of [14C]Ethane Dimethanesulfonate in Immature and Adult Male Rats Following an Acute Exposure

Abstract

Distribution of [14C]Ethane Dimethanesulfonate in Immature and Adult Male Rats Following an Acute Exposure. Laskey, J. W., Kelce, W. R., Klinefelter, G. R., Gray, L. E., Jr., and Ewing, L. L. (1994). Fundam. Appl. Toxicol. 22, 319-327.In the adult rat, ethane dimethanesulfonate (EDS) reduces testosterone (T) production by killing Leydig cells. Studies have also shown that acute EDS administration produces transient infertility and epididymal effects. Although these later effects were believed to be indirect results of the reduced Leydig cell T production, it was recently found that the epididymal effects were partially a direct result of in vivo EDS treatment. In contrast to the Leydig cells of the adult rat, immature Leydig cells are affected by EDS only at doses four- to sixfold higher than those that affect mature Leydig cells. In fact, the Leydig cells of the adult rat seem to be uniquely susceptible to the cytotoxic effects of EDS. Steroidogenesis in other organs, like the adrenal and ovary, are unaffected in vivo at doses that eliminate T production in males. In addition, studies have shown that doses of EDS that kill Leydig cells in vitro , isolated from the testes of adult rats, have no effect on similarly exposed hepatocytes. Hence, it was the objective of this study to describe the distribution and temporal fate of EDS in target (testes and epididymides) and nontarget tissues in immature and adult male rats and to determine if this information would explain either the age- or tissue-related susceptibility to EDS. We have concluded from this study that tissue distribution, integrated in vivo EDS dose, and differences in EDS metabolism are not the only factors contributing to the difference in sensitivity. The information collected in this study will enable us to use in vitro EDS concentrations for examination of the mechanism of action at doses relevant to those produced in vivo.