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Apoptosis and the adaptive response in human lymphocytes
S P Cregan1, D L Brown, R E Mitchel
1Atomic Energy of Canada Limited, Chalk River Laboratories, ON.
Purpose:
To determine whether the sensitivity of human lymphocytes for apoptosis 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 donors were exposed to low doses of the DNA damaging agent gamma-radiation, or the membrane oxidizing agent t-butyl hydroperoxide (t-BuOOH), incubated for various times and then tested for their sensitivity to induction of apoptosis by a subsequent exposure to a high dose of either agent. Apoptosis was measured using a fluorescent assay of DNA unwinding or a terminal deoxynucleotide transferase assay.
Results:
The results show that Go lymphocytes pre-exposed to an adapting dose of radiation or DNA strand breaking agent are not protected but can become sensitized to subsequent apoptosis induced by radiation (a kinetically slow process). Inter- and intraindividual variations were observed. However, neither pre-exposure to radiation nor to a membrane oxidizing agent sensitized lymphocytes from any donor to apoptosis induced by a membrane oxidizing agent (a kinetically fast process).
Conclusions:
Since an increase in the elimination of genetically damaged cells by apoptosis could reduce the risk of cancer from exposure to radiation or other DNA damaging agents, this cellular sensitization for apoptosis may represent a novel adaptive response mechanism.