OXIDATIVE STRESS SUPPRESSES TRANSCRIPTION FACTOR ACTIVITIES IN STIMULATED LYMPHOCYTES

Effects of oxidative stress on stimulation-dependent signal transducti on, leading to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells were then stimulated for 6 h. DNA-binding activities (determined by the electrophoretic mobility shift assay) of three transcription factors: NF kappa B, AP-1 and NFAT , were abolished in the lymphocytes by all three modes of oxidative st ress. The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used (20 mu M). All three mod es of oxidative stress induced catalase activity in the lymphocytes. T he only exception was hydrogen peroxide at 20 mu M, which did not indu ce catalase activity. We conclude that: (i) suppression of specific tr anscription factor functions can potentially serve as a marker of expo sure to oxidative stress and its effects on human lymphocytes; (ii) li pid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity; (ii i) therefore, transcription factor DNA-binding activities are more sen sitive to oxidative stress than lipid peroxidation.