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

Abstract

Various markers of radiation-induced DNA damage including DNA oxidation were 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′deoxy-7-dihydro-8-oxoguanosine/2′deoxyguanosine (8-oxodG/dG) from 1.73×10 −5 to 3.33×10 −5. Frequencies of micronuclei significantly ( p=0.0003) increased from 6.4 to 38.9 per 1000 cells. The frequency of hypoxanthine-guanine-phosphoribosyltransferase ( HPRT) mutant lymphocytes measured as 6-thioguanine resistant variant cells by 5-bromodeoxyuridine labeling, was elevated eight-fold, from 4.7×10 −6 to 36.2×10 −6 ( p=0.008) after termination of the radiotherapy, thus showing a clear response to the radiation treatment. No correlation between levels of oxidative DNA damage and frequencies of HPRT mutant lymphocytes or micronuclei could be established.