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Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes
Authors:Angelini Sabrina  Kumar Rajiv  Carbone Fabio  Maffei Francesca  Forti Giorgio Cantelli  Violante Francesco Saverio  Lodi Vittorio  Curti Stefania  Hemminki Kari  Hrelia Patrizia
Institution:Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126, Italy. angelini@biocfarm.unibo.it
Abstract:Understanding the risks deriving from protracted exposure to low doses of ionizing radiation has remarkable societal importance in view of the large number of work settings in which sources of IR are encountered. To address this question, we studied the frequency of micronuclei (MN), which is an indicator of DNA damage, in a population exposed to low levels of ionizing radiation and in matched controls. In both exposed population and controls, the possible influence of single nucleotide polymorphisms in XRCC1, XRCC3 and XPD genes on the frequency of micronuclei was also evaluated. We also considered the effects of confounding factors, like smoking status, age and gender. The results indicated that MN frequency was significantly higher in the exposed workers than in the controls 8.62+/-2.80 versus 6.86+/-2.65; P=0.019]. Radiological workers with variant alleles for XRCC1 or XRCC3 polymorphisms or wild-type alleles for XPD exon 23 or 10 polymorphisms showed a significantly higher MN frequency than controls with the same genotypes. Smoking status did not affect micronuclei frequency either in exposed workers or controls, while age was associated with increased MN frequency in the exposed only. In the combined population, gender but not age exerted an influence on the yield of MN, being higher in females than in males. Even though there is a limitation in this study due to the small number of subjects, these results suggest that even exposures to low level of ionizing radiation could have genotoxic effects and that XRCC3, XRCC1 and XPD polymorphisms might contribute to the increased genetic damage in susceptible individuals occupationally exposed to chronic low levels of ionizing radiation. For a clear conclusion on the induction of DNA damage caused by protracted exposure to low doses of ionizing radiation and the possible influence of genetic polymorphism in DNA repair genes larger studies are needed.
Keywords:CA  chromosomal aberrations  MN  micronuclei  BER  base excision repair  HRR  homologous recombination repair  SNPs  single nucleotide polymorphisms  NER  nucleotide excision repair  EPIC  European prospective investigation into cancer and nutrition  FFQ  food frequency questionnaire  Hwb  dose equivalent of ionizing radiation to the whole body  BN  binucleated  NDI  nuclear division index  PCR-RFLP  polymerase chain reaction-restriction fragment length polymorphism  SSCP  single strand conformation polymorphism  S  D    standard deviation  FISH  fluorescence in situ hybridization
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