The Effect of Dimethyl Sulfoxide on the Induction of DNA Double-Strand Breaks in V79-4 Mammalian Cells by Alpha Particles

Abstract

The present study was undertaken to assess the protective effect of dimethyl sulfoxide (DMSO) against the induction and rejoining of DNA double-strand breaks (DSBs) and inactivation of V79-4 Chinese hamster cells by both high- and low-linear energy transfer (LET) radiations. The cells were exposed under aerobic conditions as monolayers to either low-LET photons (60Co gamma rays) or high-LET alpha particles (238Pu) at 277 K. The initial yield of DSBs, determined by elution under nondenaturing conditions, is linearly dependent on dose. When the irradiation was carried out in the presence of DMSO (0-0.6 mol dm-3), the initial yields of DSBs induced by both gamma and alpha-particle irradiation decrease. With gamma irradiation at [DMSO] > 0.6 mol dm-3, a further decrease in the yield of DSBs occurs. DMSO (0.5 mol dm-3) reduces the initial yield of DSBs by 50 +/- 5% and 32 +/- 4% for photons and alpha particles, respectively. DMSO protects more effectively against cellular inactivation and DSB induction at low LET compared with alpha-particle irradiation with protection factors of 1.7 and 1.4, respectively, for survival and 2.0 and 1.5, respectively, for DSBs. After incubation of the irradiated cells for 3 h at 310 K after high-LET irradiation, the residual yield of DSBs is reduced by < 13% when the irradiations were carried out in the presence of 0.5 mol dm-3 DMSO. With gamma irradiation in the presence of 0.5 mol dm-3 DMSO, 90% of the DSBs are rejoined by 3 h incubation at 310 K. Therefore, the nonscavengeable DSBs induced by alpha particles are not significantly rejoined within 3 h, in contrast to rejoining of the majority of the nonscavengeable DSBs induced by gamma irradiation. From comparison of the data on DSBs and survival for alpha-particle irradiation, it is inferred that the severity of damage is reduced by DMSO through minimizing the formation of OH-induced sugar/base modifications in the vicinity of nonscavengeable DSBs.