MUTANT QUANTITY AND QUALITY IN MAMMALIAN-CELLS (A(L)) EXPOSED TO CESIUM-137 GAMMA-RADIATION - EFFECT OF CAFFEINE

We examined the effect of caffeine (1,3,7-trimethylxanthine) on the qu antity and quality of mutations in cultured mammalian A(L) human-hamst er hybrid cells exposed to Cs-137 gamma radiation. At a dose (1.5 mg/m l for 16 h) that reduced the plating efficiency (PE) by 20%, caffeine was not itself a significant mutagen, but it increased by approximatel y twofold the slope of the dose-response curve for induction of S1(-) mutants by Cs-137 gamma radiation. Molecular analysis of 235 S1(-) mut ants using a series of DNA probes mapped to the human chromosome 11 in the A(L) hybrid cells revealed that 73 to 85% of the mutations in une xposed cells and in cells treated with caffeine alone, Cs-137 gamma ra ys alone or Cs-137 gamma rays plus caffeine were large deletions invol ving millions of base pairs of DNA. Most of these deletions were conti guous with the region of the MIC1 gene at 11p13 that encodes the S1 ce ll surface antigen. In other mutants that had suffered multiple marker loss, the deletions were intermittent along chromosome 11. These ''co mplex'' mutations were rare for Cs-137 gamma irradiation (1/63 = 1.5%) but relatively prevalent (23-50%) for other exposure conditions. Thus caffeine appears to alter both the quantity and quality of mutations induced by Cs-137 gamma irradiation. (C) 1995 by Radiation Research so ciety