Insertions have been proposed as potential stable biomarkers of chronic high-LET radiation exposure. To examine this in vitro, we irradiated human peripheral blood lymphocytes in G(0) with either 50 cGy (238)Pu alpha particles (LET 121.4 keV/microm) or 3 Gy 250 kV X rays and stimulated their long-term culture up to approximately 22 population doublings postirradiation. Mitotic cells were harvested at regular intervals throughout this culture period and were assayed for chromosome aberrations using the techniques of three-color and 24-color mFISH. We observed the stable persistence of transmissible-type complex rearrangements, all involving at least one insertion. This supports the hypothesis that insertions are relevant indicators of exposure to high-LET radiation. However, one practical caveat of insertions being effective biomarkers is that their frequency is low due to the complexity and cell lethality of the majority of alpha-particle-induced complexes. Therefore, we propose a "profile of damage" that relies on the presence of insertions, a low frequency of stable simple reciprocal translocations (2B), and, significantly, the complexity of the damage initially induced. We suggest that the complexity of first- and second-division alpha-particle-induced nontransmissible complex aberrations reflects the structure of the alpha-particle track and as a consequence adds radiation-quality specificity to the biomarker, increasing the signal:noise ratio of the characteristic 2B:insertion ratio.

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.

We undertook an analysis of chromosome-type exchange aberrations induced by alpha-particles using fluorescence in situ hybridization (FISH) with whole chromosome-specific probes for human chromosomes 1 or 4, together with a pan-centromeric probe. Contact-inhibited primary human fibroblasts (in G1) were irradiated with 0.41-1.00 Gy 238Pu alpha-particles and aberrations were analysed at the next mitosis following a single chromosome paint. Exchange and aberration painting patterns were classified according to Savage and Simpson (1994a). Of exchange aberrations, 38-47% were found to be complex derived, i.e. resulting from three or more breaks in two or more chromosomes, and the variation with dose was minimal. The class of complex aberrations most frequently observed were insertions, derived from a minimum of three breaks in two chromosomes. There was also an elevated frequency of rings. The high level of complex aberrations observed after alpha-particle irradiation indicates that, when chromosome domains are traversed by high linear energy transfer alpha-particle tracks, there is an enhanced probability of production of multiple localized double-strand breaks leading to more complicated interactions.