DISTRIBUTION OF [C-14] ETHANE DIMETHANESULFONATE IN IMMATURE AND ADULT MALE-RATS FOLLOWING AN ACUTE EXPOSURE

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 re sults of the reduced Leydig cell T production, it was recently found t hat the epididymal effects were partially a direct result of in vivo E DS treatment. In contrast to the Leydig cells of the adult rat, immatu re Leydig cells are affected by EDS only at doses four- to sixfold hig her than those that affect mature Leydig cells. In fact, the Leydig ce lls 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 Ley dig cells in vitro, isolated from the testes of adult rats, have no ef fect on similarly exposed hepatocytes. Hence, it was the objective of this study to describe the distribution and temporal fate of EDS in ta rget (testes and epididymides) and nontarget tissues in immature and a dult male rats and to determine if this information would explain eith er 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 contribut ing to the difference in sensitivity. The information collected in thi s study will enable us to use in vitro EDS concentrations for examinat ion of the mechanism of action at doses relevant to those produced in vivo. (C) 1994 Society of Toxicology.