INDUCTION OF THERMOTOLERANCE IN EARLY POSTIMPLANTATION RAT EMBRYOS ISASSOCIATED WITH INCREASED RESISTANCE TO HYPERTHERMIA-INDUCED APOPTOSIS

Previously we reported that hyperthermia (43 degrees C) induces cell d eath in neurulation stage rat embryos as part of the pathogenesis culm inating in abnormal growth and development. We now show that hyperther mia-induced cell death occurs by a process termed apoptosis. DNA fragm entation, a hallmark of apoptosis, was noted as early as 2.5 hr after embryos were exposed to 43 degrees C. A smaller but significant increa se in DNA fragmentation was also observed in embryos exposed to 42 deg rees C, but only at the 5 hr time point. In control embryos, TUNEL-pos itive apoptotic bodies were consistently observed in the neuroepitheli um at the point of neural tube closure and in the optic stalk, In embr yos exposed to 43 degrees C, the number of TUNEL-positive apoptotic bo dies was significantly increased. Using both gel electrophoresis and T UNEL, we also show that the induction of thermotolerance is associated with a significant reduction in DNA fragmentation. Together our resul ts show that specific programmed cell death and hyperthermia-induced c ell death correlate with internucleosomal DNA fragmentation characteri stic of apoptosis. Finally, we show that the induction of thermotolera nce in rat embryos is associated with a significant reduction in inter nucleosomal DNA fragmentation and associated apoptosis. (C) 1997Wiley- Liss, Inc.