Apoptosis and the adaptive response in human lymphocytes

Purpose: To determine whether the sensitivity of human lymphocytes for apop tosis induced by either a membrane oxidizing agent or a DNA damaging agent is modified by an adaptive response. Materials and methods: Peripheral blood lymphocytes from normal human donor s were exposed to low doses of the DNA damaging agent gamma-radiation, or t he membrane oxidizing agent t-butyl hydroperoxide (t-BuOOH), incubated for various times and then tested for their sensitivity to induction of apoptos is by a subsequent exposure to a high dose of either agent. Apoptosis was m easured using a fluorescent assay of DNA unwinding or a terminal deoxynucle otide transferase assay. Results: The results show that G(o) lymphocytes pre-exposed to an adapting dose of radiation or DNA strand breaking agent are not protected but can be come sensitized to subsequent apoptosis induced by radiation (a kinetically slow process). Inter- and intraindividual variations were observed. Howeve r neither preexposure to radiation nor to a membrane oxidizing agent sensit ized lymphocytes from any donor to apoptosis induced by a membrane oxidizin g agent (a kinetically fast process). Conclusions: Since an increase in the elimination of genetically damaged ce lls by apoptosis could reduce the risk of cancer from exposure to radiation or other DNA damaging agents, this cellular sensitization for apoptosis ma y represent a novel adaptive response mechanism.