The combined effects of alpha-particles and X-rays on cell killing and micronuclei induction in lung epithelial cells

Understanding how cellular damage produced by high-linear energy transfer (LET) radiation interacts with that produced by low-LET is important both in radiation therapy and in evaluating risk. To study such interactions, rat lung epithelial cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and alpha-particles given separately caused dose-related increases in cell cycle time, with alpha-particles producing greater mitotic delay than X-rays. Damage from alpha-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and alpha-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha-particles plus graded X-ray doses, were adequately described using only the linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/- 0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007 +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers of micronuclei produced by exposure to alpha-particles or X-rays alone increased linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05 micronuclei/binucleated cell per Gy for alpha and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant alpha dose of either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/- 0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These slopes are similar to that produced by alpha-particles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposures compared with that predicted for separate exposures.