HPRT MUTATIONS IN HUMAN T-LYMPHOCYTES REFLECT RADIOPROTECTIVE EFFECTSOF THE AMINOTHIOL, WR-1065

Aminothiols such as WR-2721 and its active free thiol WR-1065 have pre viously been shown to reduce mutations resulting from ionizing radiati on in exponentially growing cells, In this study, non-dividing human G o T-lymphocytes were exposed to the aminothiol radioprotective agent, WR-1065, 30 min before or 3 h after external beam gamma-irradiation an d subsequently assessed for survival and mutation induction at the hpr t locus, Cytotoxicity due to gamma-irradiation was reduced only when t he WR-1065 was present during irradiation, The frequency of hprt mutat ions, however, was reduced regardless of time of administration, altho ugh the reduction was statistically significant only when WR-1065 was added 30 min before irradiation (P < 0.01), This is the first study to demonstrate the protective effects of WR-1065 against radiation-induc ed mutation in a reporter gene using a human non-cycling cell, Hprt mu tations arising in vivo in these cells may be useful for monitoring th e radioprotective effect of aminothiols in human populations.