Mutation induction by continuous low dose rate gamma irradiation in human cells

Human teratocarcinoma cells P3 were subjected to 60 Co-gamma-rays in continuous exponential growth using a "chemostat" set-up. Mutations at the HPRT-locus were measured with dose rates of 5 mGy/h, 50 mGy/h and after acute exposure. There was a clear reduction of mutation induction efficiency with 50 mGy/h compared to the high dose rates, however, with 5 mGy/h the same results were obtained as with acute exposure, in other words mutation induction increased again with very low dose-rates. This phenomenon of an "inverse dose rate effect" is restricted to cycling cells, as it was not found in plateau phase cells exposed under identical conditions. These results confirm previous findings by others and us in rodent cells, which were so far not available for human cells. In order to explore a possible contribution of "genomic instability", cells irradiated acutely with a dose of 3 Gy were grown for up to 40 days in an exponential culture, and the mutant frequencies were determined every second day. A rise in mutant frequency after 20-30 days was consistently found in three independent experiments but time course and mutant numbers were not reproducible and seemed to follow a stochastic behaviour. The results cast doubt on the common assumption that a reduction in the dose rate will always lead to smaller effects, although this somewhat artificial system cannot be generalised to the human situation. (C) 2002 Elsevier Science B.V All rights reserved.