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

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 (${}^{60}{\rm Cs}$ γ rays) or high-LET α particles (${}^{238}{\rm Pu}$) 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 ($0-0.6\ {\rm mol}\ {\rm dm}^{-3}$), the initial yields of DSBs induced by both γ and α-particle irradiation decrease. With γ irradiation at [DMSO] >$0.6\ {\rm mol}\ {\rm dm}^{-3}$, a further decrease in the yield of DSBs occurs. DMSO ($0.5\ {\rm mol}\ {\rm dm}^{-3}$) reduces the initial yield of DSBs by 50 ± 5% and 32 ± 4% for photons and α particles, respectively. DMSO protects more effectively against cellular inactivation and DSB induction at low LET compared with α-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$0.5\ {\rm mol}\ {\rm dm}^{-3}$ DMSO. With γ irradiation in the presence of$0.5\ {\rm mol}\ {\rm dm}^{-3}$ DMSO, 90% of the DSBs are rejoined by 3 h incubation at 310 K. Therefore, the nonscavengeable DSBs induced by α particles are not significantly rejoined within 3 h, in contrast to rejoining of the majority of the nonscavengeable DSBs induced by γ irradiation. From comparison of the data on DSBs and survival for α-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.