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 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 x 10(-5) to 3.33 x 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 x 10(-6) to 36.2 x 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.
Zwingmann
I H
IH
Department of Health Risk Analysis and Toxicology, Maastricht University, Netherlands.
Welle
I J
IJ
Engelen
J J
JJ
Schilderman
P A
PA
de Jong
J M
JM
Kleinjans
J C
JC
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D001973:Bromodeoxyuridine / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000528:radiation effects; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D012907:Smoking
D000975:Antioxidants; D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007041:Hypoxanthine Phosphoribosyltransferase; D001973:Bromodeoxyuridine; D003849:Deoxyguanosine