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AbstractThe ability to repair DNA damage is strongly associated with the risk of cancer and other human diseases as it is essential for maintenance of genome stability. Moreover, DNA repair capacity is an important factor contributing to the inter-individual variability in mutagen exposure, cancer development and treatment through an individualized adjusted therapy. In addition to genotypes, functional phenotypic assays which integrate the different pathways provide useful tools to explore the role of DNA repair in cancer susceptibility. This review compares the presently available cellular DNA repair phenotype assays based on their characteristics, and discusses their advantages and limitations. Assays for assessment of DNA repair phenotype should be well characterized in terms of reliability, validity, sensitivity, inter- and intra-individual variability, and cancer predictivity. Our comparison reveals that the G₁ and G₂ challenge assays, although labour-intensive, can be considered as very useful assays to investigate DNA repair phenotype. They have been successfully applied to investigate repair capacity of both cancer patients and environmentally exposed populations, and can detect deficiencies in different repair pathways. Moreover, these assays allow to predict the cancer therapy responses and to investigate the cancer prognosis. Nevertheless, the choice of the assay depends on the scientific question addressed and on the objective of its application and more prospective studies are needed since the phenotype could reflect the pathophysiological alterations in the patient secondary to the disease.
CitationMutat. Res. 2010, 705 (2):107-129
SponsorsThis work was supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:‘‘Food Quality and Safety’’(Contract No 513943) and by the EU Integrated Project NewGeneris, 6th Framework Programme, Priority 5:Food Quality and Safety (Contract no. FOOD-CT-2005- 016320). NewGeneris is the acronym of the project ‘Newborns and Genotoxic exposure risks’.
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