A comparison of somatic mutational spectra in healthy study populations from Russia, Sweden and USA Page: 4 of 30
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Comparison of mutation spectra at the hypoxanthine-phosphoribosyl transferase (HPRT)
gene of peripheral blood T lymphocytes may provide insight into the aetiology of somatic
mutation contributing to carcinogenesis and other diseases. To increase knowledge of
mutation spectra in healthy people, we have analysed HPRT mutant T-cells of 50 healthy
Russians originally recruited as controls for a study of Chernobyl clean-up workers
(Jones et al. Radiation Res. 158, 2002, 424). Reverse transcriptase polymerase chain
reactions and DNA sequencing identified 161 independent mutations among 176
thioguanine resistant mutants. Forty (40) mutations affected splicing mechanisms and 27
deletions or insertions of 1 to 60 nucleotides were identified. Ninety four (94) single base
substitutions were identified, including 62 different mutations at 55 different nucleotide
positions, of which 19 had not previously been reported in human T-cells. Comparison of
this base substitution spectrum with mutation spectra in a USA (Burkhart-Schultz et al.
Carcinogenesis 17, 1996, 1871) and two Swedish populations (Podlutsky et al,
Carcinogenesis 19, 1998, 557, Podlutsky et al. Mutation Res. 431, 1999, 325) 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 pair-wise 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 Adams and Skopek (J. Mol. Biol. 194, 1987, 391) 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
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Noori, P; Hou, S; Jones, I M; Thomas, C B & Lambert, B. A comparison of somatic mutational spectra in healthy study populations from Russia, Sweden and USA, article, October 27, 2004; Livermore, California. (digital.library.unt.edu/ark:/67531/metadc875338/m1/4/: accessed January 22, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.