The Combined Effects of α-particles and X-rays on Cell Killing and Micronuclei Induction in Lung Epithelial Cells

Abstract

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 α-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and α-particles given separately caused dose-related increases in cell cycle time, with α-particles producing greater mitotic delay than X-rays. Damage from α-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and α-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to α-particles only, or to 1·0 Gy α-particles 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 α-particles 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 α-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 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 α-particles 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.