EFFECT OF SIGNAL-TRANSDUCTION INHIBITION IN ADAPTED LYMPHOCYTES - MICRONUCLEI FREQUENCY AND DNA-REPAIR

Irradiation of human lymphocytes (1 cGy X rays, 37 degrees C) or their treatment with 10 mu M hydrogen peroxide (30 min at 37 degrees C) evo ked a ca 30% decrease in the frequency of micronuclei upon subsequent X-irradiation (1.5 Gy). The response was reflected in a lower micronuc lei frequency, but no change in DNA repair rate was observed as measur ed by the comet assay, directly after the challenge dose. Treatment of lymphocytes with staurosporine, an inhibitor of protein kinases, or w ith TMB-8, a calcium antagonist, carried out in parallel with the adap tive dose prevented the development of the adaptive response measured as micronuclei frequency. In lymphocytes that were staurosporine- or T MB-8-treated and irradiated under adaptive conditions showed that the rate of DNA repair was not changed. We conclude that treatment with ag ents that interfere with the transduction of the signal triggered by t he low dose prevents the development of the adaptive response induced by X rays or hydrogen peroxide. Lower chromosome damage revealed by th e cytokinesis block-micronuclei test in the adapted lymphocytes is unr elated to DNA repair rate as measured by comet assay.