OXYGEN RADICALS INDUCE STRESS PROTEINS AND TOLERANCE TO OXIDATIVE STRESS IN HUMAN-LYMPHOCYTES

set of eight proteins is induced in peripheral blood lymphocytes from normal donors by exposure to hydrogen peroxide or to xanthine oxidase plus hypoxanthine. Four of them (hsp90, hsp72 and proteins 65 and 50 k Da) are also expressed after heat shock, together with proteins 110, 1 00 and 38 kDa. Among proteins induced after oxidative stress is a 32 k Da protein-probably corresponding to heme oxygenase-l (HO-l)-and a 27 kDa protein, both known to be induced by reactive oxygen species. Alth ough ionizing radiation is known to generate a number of pro-oxidant i ntermediates, using our one-dimensional electrophoresis system we can detect no differences in the proteins synthesized after exposure to ga mma-ray doses between 5 and 20 Gy as compared with control cells. Pre- exposure to a mild hyperthermia or to moderate oxidative stress signif icantly increases survival of lymphocytes challenged with high doses o f reactive oxygen species, in conditions compatible with a protective role exerted by stress proteins. The increase in survival is accompani ed by the maintenance of the proliferative capacity of the cells. The physiological role played by stress proteins in prevention and repair of damage and the relationships between stress protein induction, oxid ative state, proliferation and mode of cell death are discussed.