REGULATION OF SIGNAL-TRANSDUCTION AND DNA FRAGMENTATION IN THYMOCYTES BY ETHANOL

We demonstrated previously that ethanol enhances apoptosis of murine thymocytes. In this report, we determined intracellular cAMP and cytosolic free calcium ([Ca2+](i)) levels in mouse thymocytes following acute exposure to ethanol and investigated the involvement of cAMP, [Ca2+](i), protein kinase A (PKA), and protein kinase C (PKC) in thymocyte apoptotic death induced by ethanol. It was found that ethanol did not alter basal cAMP levels, but produced a dose-dependent, prolonged small [Ca2+](i) increase within thymocytes. This dose dependence of [Ca2+](i) increase was paralleled by the magnitude of DNA fragmentation induced by ethanol at various concentrations. Additionally, the ethanol-enhanced DNA fragmentation was blocked by H7, a PKC inhibitor, but not by potent PKA inhibitors having little or no effect on PKC. These data suggest that both [Ca2+](i) increase and PRC activation triggered by ethanol may belong to the signal pathway(s) leading to thymocyte programmed death. (C) 1995 Academic Press, Inc.