1887

Abstract

Abstract

In the Republic of Kazakhstan, during the period between 1949 and 1989, nuclear weapon testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (STS) resulted in local fallout affecting the residents of East Kazakhstan. The STS has been the site for more than 450 nuclear tests, including 26 on the ground and 87 atmospheric explosions. It is estimated that there are about 500,000 A-bomb victims around STS. These individuals have been repeatedly exposed to ionizing radiation from the radioactive cloud or environmental fallout for many years. To gain insight into the health concerns of the exposed population, we carried out a molecular genetic study to estimate health risk in a three-generation (Р0,F1,F2) sample from the STS population. We previously reported a 1.8-fold increase in minisatellite mutation (MM) rate in the exposed Р0 generation. Our results indicated that the radiation exposure from the nuclear tests had caused elevated MM rates and germ-line mutations. Although the underlying mechanisms for the instability are not known, the MM are considered as originating from genomic instability induced by radiation exposure. We further investigated the influence of polymorphisms in genes on the expression of MM in three generations of the exposed and control populations and the relationship between radiation exposure and MM expression. We chose the analyses of three polymorphic DNA-repair genes (XRCC1, XRCC2 and XRCC3) and two xenobiotic detoxification genes (GSTT1 and GSTM1). It was shown that among the exposed and in comparison with the wild-type gene, the functionally active XRCC1 Arg194Trp was significantly associated with low MM and over-represented in the exposed compared with the control populations. In a similar analysis, the functionally deficient XRCC1 Arg399Glu and XRCC3 Trp241Met were associated with increased and significantly reduced MM, respectively, but these variant genes were underrepresented in the exposed population. Both GSTT1 and GSTM1 nulls were significantly associated with increased MM. In summary, our results showed the role of susceptibility genes on the expression of MM in three generations of radiation-exposed population and the complexity of gene and environment interactions on health risk assessment.

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/content/papers/10.5339/qproc.2012.mutagens.3.11
2012-03-01
2019-10-14
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.11
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  • Received: 07 May 2012
  • Accepted: 07 May 2012
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