Differences in DNA Damage and DNA Repair Capacities as Transient Biomarkers of Colorectal Carcinogen

来源 :BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会) | 被引量 : 0次 | 上传用户:fiveboy0714
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  Human DNA repair protects the integrity of the genome and ensures the general and specialized functions of cells,thus preventing the carcinogenesis.Consequently, differences in DNA repair efficiency pose an important issue in sporadic cancer (e.g.colorectal;CRC;) etiology, affected by complex gene-environment interactions.DNA repair capacity measurements (functional DNA repair assays) represent a complex marker integrating genetic polymorphisms,gene expression, stability of gene product, effect of inhibitors/stimulators, environmental factors and lifestyle factors.Further, functional DNA repair assays reflect the capacity of the organism to cope with a chronic exposure to numerous environmental and dietary genotoxicants and may be used as predictive markers in cancer therapy.Hereby we report a functional test for nucleotide excision repair capacities (NER) in relation to polymorphisms in genes involved in NER.Levels of DNA damage and NER capacities were determined in lymphocytes of 70 incident CRC patients, before undergoing any treatment and matched 70 healthy controls.We have observed significant differences in both analyzed parameters.While CRC patients showed a higher level of DNA damage (median: 25.9 versus 9.3 tail DNA%, p<0.001),they simultaneously exhibited a considerably lower NER capacities (median: 8.7 versus 12.9 tail DNA%, p<0.001).mRNA levels and allelic vartiants in genes involved in incidion phase of DNA repair were assayed for.The same CRC patients have been followed up with respect to their anticancer treatment and above repair characteristics have been recorded.Both base-excision (BER) and NER capacities have been analyzed in blood cells, healthy mucosa and tumor tissue samples of 19 patients with sporadic CRC.In contrast to lymphocytes, tumor tissue exhibited the highest BER and NER capacities.The definition of genetic and phenotypic landscape of the disease is further extended by DNA repair functional characteristics, both on the surrogate (systemic) and target tumor (topical level) tissue.The role of DNA excision repair in the response to chemotherapy has been also addressed.
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