Genotoxicity of the space environment




Khaidakov, Magomed

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This thesis presents a study on possible genetic consequences of the exposure to the space environment during space missions The present study was undertaken in co-operation with the Canadian Space Agency, and involved the analysis of the lymphocyte samples taken from experienced cosmonauts and trainees. For the analysis of genotoxicity of the space environment, a T-lymphocyte hprt clonal assay has been employed. In order to distinguish between artefacts associated with this method and the spaceflight-related effects, we have conducted a series of in vitro reconstruction experiments. In these experiments we have analysed interactions between plating efficiency (PE) of T-lymphocytes and efficiency of mutant recovery. Using 12 pairs of independent wild type (WT) and mutant clones, we have demonstrated an inverse correlation between initial viability of the WT cells and survival of mutant cells (r = 0.3496, p < 0.05). Our data suggest that the presence of WT cells in the selection plates does suppress the recovery of mutants in HPRT assay. This effect is stronger in samples with high PE, and may be a source of large error in estimation of mutant frequencies (approx. 3-fold in the range of PEs from 10% to 60%), which is especially relevant when samples with different PEs are compared. Analysis of samples from cosmonauts was conducted in two experiments. The first experiment involved 5 samples taken in 1992 from cosmonauts who have completed spaceflights ranging in duration from 7 to 365 days. Hprt mutant frequencies (MF) in these samples were 2.5–5 times higher than the age-corrected values for healthy, unexposed subjects in Western countries (Tates et al., 1991; Branda et al., 1993), and 2-3-fold higher than those determined for unexposed individuals residing in Russia (Jones et al., 1995). The cosmonaut mutational spectrum differed from that of unexposed healthy subjects (p = 0.042), and showed a higher incidence of splicing errors, frameshifts, and complex mutations. Distribution of base substitutions was remarkably similar to that observed in Russian twins sampled at the same period (Curry et al., 1998), thus suggestive of possible environmental, diet, or life-style related exposures. The second study was conducted on samples taken 5 years later and involved trainees and a group of cosmonauts with more uniform (at least 6 months) and recent flight experience. Hprt MFs in both cosmonaut and trainee groups were virtually identical (17.2 ± 0.6 and 17.6 ± 4.7 × 10⁻⁶ respectively), and approximately 2-fold higher than in matching Western controls, although considerably lower than in our previous observations. Mutational spectra in both datasets were very similar to that observed in our earlier study, and were significantly different from spontaneous data (p = 0.031–0.038). Distribution of base substitutions, however, did not show any differences. Our data indicate that the space environment is not genotoxic at the hprt locus. At the same time, uniformly high MFs observed in all studied groups suggest that the level of the mutagenic burden in at least megalopolis areas of Russia may be considerably larger than in the West. Also, there are some indications of a possible restructuring of mutagenic burden in post-transitional Russia.



Genetic toxicology, Space environment