A comparison of somatic mutational spectra in healthy study populations from Russia, Sweden and USA.
A comparison of mutation spectra at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene of peripheral blood T-lymphocytes may provide an insight into the aetiology of somatic mutation contributing to carcinogenesis and other diseases. To increase the knowledge of mutation spectra in healthy people, we have analysed HPRT mutant T-cells of 50 healthy Russians originally recruited as controls in a study involving Chernobyl clean-up workers [I.M. Jones, H.Galick, P.Kato et al. (2002) Radiat. Res., 158, 424-442]. Reverse transcriptase-polymerase chain reactions and DNA sequencing identified 161 independent mutations among 176 thioguanine-resistant mutants. Forty mutations affected splicing mechanisms and 27 deletions or insertions of 1-60 nt were identified. Ninety-four single base substitutions were identified, including 62 different mutations at 55 different nucleotide positions, of which 19 had not been reported previously in human T-cells. Comparison of this base substitution spectrum with mutation spectra in a USA [K.J.Burkhart-Schultz, C.L. Thompson and I.M. Jones (1996) Carcinogenesis, 17, 1871-1883] and two Swedish populations [A.Podlutsky, A.-M.Osterholm, S.-M.Hou, A. Hofmaier and B. Lambert (1998) Carcinogenesis, 19, 557-566; A.Podlutsky, S.M.Hou, F.Nyberg, G. Pershagen and B. Lambert (1999) Mutat. Res., 431, 325-39] revealed similarity in the type, frequency and distribution of mutations in the four spectra, consistent with aetiologies inherent in human metabolism. There were 15-19 identical mutations in the three pairwise comparisons of Russian with USA and Swedish spectra. Intriguingly, there were 21 mutations unique to the Russian spectrum, and comparison by the Monte Carlo method of W.T. Adams and T.R. Skopek [(1987) J. Mol. Biol., 194, 391-396] indicated that the Russian spectrum was different from both Swedish spectra (P = 0.007, 0.002), but not different from the USA spectrum (P = 0.07) when Bonferroni correction for multiple comparisons was made (P < 0.008 required for significance). Age and smoking did not account for these differences. Other factors causing mutational differences need to be explored.
Noori
Peri
P
Department of Biosciences, The Karolinska Institute, Novum, SE-14157 Huddinge, Sweden.
Hou
Saimei
S
Jones
Irene M
IM
Thomas
Cynthia B
CB
Lambert
Bo
B
D000328:Adult; D000367:Age Factors; D001483:Base Sequence; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016273:Occupational Exposure / Q000009:adverse effects; D012426:Russia; D012907:Smoking / Q000009:adverse effects; D013548:Sweden; D013601:T-Lymphocytes / Q000201:enzymology*; D014481:United States
D007041:Hypoxanthine Phosphoribosyltransferase