A comparison of somatic mutational spectra in healthy study populations from Russia, Sweden and USA

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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 analyzed 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 ... continued below

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Noori, P; Hou, S; Jones, I M; Thomas, C B & Lambert, B October 27, 2004.

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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 analyzed 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 explored.

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PDF-file: 30 pages; size: 0.2 Mbytes

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  • Journal Name: Carcinogenesis; Journal Volume: 26

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  • Report No.: UCRL-JRNL-207512
  • Grant Number: W-7405-ENG-48
  • Office of Scientific & Technical Information Report Number: 875936
  • Archival Resource Key: ark:/67531/metadc875338

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  • October 27, 2004

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  • Sept. 21, 2016, 2:29 a.m.

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  • Dec. 6, 2016, 7:49 p.m.

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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/: accessed November 19, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.