Development of the methods to detect enzyme activities of proteins involved in repair of DNA double strand breaks

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The presence of genomic instability in cells is known to play an important role in the multistage carcinogenesis of various organs. The DNA double strand breaks(DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role in DNA DSBs repair. The purpose of this study was to determine how DNA-PK activity varies among untreated cancer patients and cancer-free normal healthy volunteers and how this affects cancer risk. DNA-PK activities of peripheral blood lymphocytes(PBL) in normal volunteers were 15.84±4.87 pmol and those of cancer patients were 12.28±5.10 pmol. There was the significant difference between them (p=0.012). Age and smoking had no association with DNA-PK activity. No association was found between DNA-PK activity and expression of DNA-PKcs, ku70, and ku86. A relationship between DNA-PK acitvity and chromosome aberration in PBL was shown to exist. Dicentric chromosomes were not observed in individuals whose DNA-PK activity was higher than 16.32 pmol. The frequency of excess fragment increased as the DNA-PK activity decreased. We conclude that DNA-PK activity is associated with chromosomal instability. DNA-PK activity in PBL is associated with risk of various kinds of cancer. Therefore, DNA-PK activity in PBL would be useful as a tumor marker to assist in the diagnosis of cancer and in the prediction of cancer susceptibility.