Analysis of oxidative DNA damage and HPRT mutant frequencies in cancer patients before and after radiotherapy

Various markers of radiation-induced DNA damage including DNA oxidation wer e investigated in peripheral lymphocytes of 23 cancer patients prior to and one week after receiving radiotherapy with a cumulative dose of 54-70 Gy. Exposure to ionizing radiation nonsignificantly increased the ratio 2' deox y-7-dihydro-8-oxoguanosine/2'deoxyguanosine (8-oxodC/dC) from 1.73 X 10(-5) to 3.33 X 10(-5). Frequencies of micronuclei significantly (p = 0.0003) in creased from 6.4 to 38.9 per 1000 cells. The frequency of hypoxanthine-guan ine-phosphoribosyltransferase (HPRT) mutant lymphocytes measured as 6-thiog uanine resistant variant cells by 5-bromodeoxyuridine labeling, was elevate d eight-fold, from 4.7 X 10(-6) to 36.2 X 10(-6) (p = 0.008) after terminat ion of the radiotherapy, thus showing a clear response to the radiation tre atment. No correlation between levels of oxidative DNA damage and frequenci es of HPRT mutant lymphocytes or micronuclei could be established. (C) 1999 Elsevier Science B.V. All rights reserved.