MOLECULAR ANALYSIS OF MUTATIONS IN T-LYMPHOCYTES FROM EXPERIENCED SOVIET COSMONAUTS

Somatic mutation in Five cosmonauts who have completed spaceflights of 7 to 365 days was analyzed using the clonal HPRT assay. The doses rec eived in space by the cosmonauts ranged from 4 to 127 mGy. hprt mutant frequencies were 2.4-5.0-fold higher than age-corrected values establ ished For healthy, unexposed subjects in western countries [Tates et a l. (1991): Mutat Res 253:199-213; Branda et al. (1993): Mutat Res 285: 267-279] and 2- to S-fold higher than those determined for unexposed i ndividuals residing in Russia [Jones et al. (1995): Mutat Res 338:129- 139]. A total of 107 collected mutant clones were analyzed by multiple x PCR. No excess of deletions wets detected and their Frequency did no t correlate with either accumulated dose or the age of the cosmonauts. In 62 mutants cDNA was isolated by RT-PCR and sequenced. Those with s plicing errors, as well as the mutants that did not produce cDNA, were Further analyzed by the sequencing of exon(s)-containing fragments am plified from genomic DNA. The mutational spectrum recovered from the c osmonauts differed substantially from that of unexposed healthy subjec ts (P = 0.042), and exhibited an increased incidence of splicing error s, frameshifts, and complex mutations. Higher frequencies of contribut ion of AT --> GC transitions and GC --> TA transversions were also obs erved. The increased mutant frequencies and observed shifts in mutatio nal spectra likely indicate a combination of potential influences, inc luding environment, lifestyle, and occupational exposures. Further elu cidation of these potential influences will re!quire a more extensive study involving the general population sharing similar environment, co smonauts in training and cosmonauts participating in space Flights. (C ) 1997 Wiley-Liss, Inc.