Induction and Rejoining of DNA Double-strand Breaks in V79-4 Mammalian Cells Following γ- and α-irradiation

Abstract

The induction and rejoining of DNA double-strand breaks (dsbs) in V79-4 mammalian cells following irradiation by ⁶⁰Co γ-rays and ²³⁸Pu α-particles (average LET 120 keV µm⁻¹) under aerobic conditions have been determined using both the sucrose sedimentation and filter elution techniques under non-denaturing conditions. Cellular inactivation was also determined. The dependence of the initial yield of dsbs at 277 K on dose under aerobic conditions is linear with a relative biological effectiveness (RBE) for α-particles of 0·85 ± 0·14 (sedimentation) and 0·68 ± 0·12 (elution) compared with ⁶⁰Co γ-rays. The ability of the cells to rejoin dsbs at 310 K is significantly reduced for α-irradiations with only 30–50% rejoined for a 3-h incubation period. With low LET radiation, > 90% of the dsbs are rejoined within 3 h at a dose of 20 Gy. The RBE for cellular inactivation was determined to be 4·0 at the 1% survival level. From the cellular dimensions and the D₀-value for cellular inactivation by α-particles, it is determined that, on average, 4·7 tracks traverse the cell nucleus per lethal lesion. Under hypoxic conditions, the RBE values for induction of dsbs and cellular inactivation (10% level) by α-particles are ∼ 3·0 and ∼ 11·8 respectively. From these findings, it is suggested that the residual DNA damage and not the initial damage is reflected in the cellular inactivation. It is inferred that the difference in repair of the various lesions is a reflection of the differences in the complexity of the clustered damage produced by these radiations.