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 αparticles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and αparticles given separately caused dose-related increases in cell cycle time, with αparticles producing greater mitotic delay than X-rays. Damage from αparticles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and αparticles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to αparticles only, or to 1.0 Gy αparticles plus graded X-ray doses, were adequately described using only the linear (α term of a linear-quadratic model with α 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 αparticles combined with X-rays was best fitted using both α and β 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 αparticles 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 α and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant α 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 αparticles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposure compared with that predicted for separate exposures. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.