Dose-rate effects of neutrons and gamma-rays on the induction of mutation and oncogenic transformation in plateau-phase mouse m5S cells.

The dose-rate effect of 252-californium neutrons was investigated using confluent cultures of mouse m5S cells. The relative biological effectiveness (RBE) of neutrons for oncogenic transformation was increased from 3.3 to 5.1 when the dose-rate was reduced from 1.8 to 0.12 cGy/min. Similarly, neutron RBE values for HPRT- mutation were 4.9 and 7.4 at dose-rates of 1.8 and 0.12 cGy/min, respectively. The increases in RBE as dose-rate was reduced were due mainly to diminished transformation- and mutation-induction by gamma-rays (the standard radiation). The yields of neutron-induced oncogenic transformation as well as neutron-induced mutation were constant for both dose rates. Our observation contrasts with reports by others using proliferating cells where both oncogenic transformation and mutation were enhanced with neutron exposure at a reduced dose-rate, the so-called inverse dose-rate effect. Since m5S cells are sensitive to postconfluent inhibition of cell division, this observation could be ascribed to cell growth conditions used in these experiments. The mechanism of the inverse dose-rate effect of neutrons suggests that the enhancement of neutron-induced mutation and oncogenic transformation at a reduced dose-rate is strongly associated with cell proliferation during exposure.