Effect of ex vivo hyperthermia on radiation-induced micronuclei in lymphocytes of cancer patients before and during radiotherapy

Abstract

To investigate the effect of ex vivo hyperthermia (HT) and 137 Cs -irradiation on micronucleus (MN) production in cytokinesis-blocked lymphocytes, we obtained the peripheral blood samples from the same cancer patients ( n=6) before and during fractionated partial-body radiotherapy (xRT). The whole blood cultures were heated at 43.5°C for 60 min, followed by 137 Cs irradiation (0–4 Gy). The control cultures from the same patients were incubated at 37°C after being exposed to radiation. The lymphocytes were then stimulated with PHA. Cytochalasin B was applied at 44 h, and lymphocytes were harvested at 72 h. MN frequency was determined on Giemsa-stained slides. We found that in patients before xRT, HT (43.5°C) significantly increased the MN yield (mean±SEM) in unirradiated lymphocytes from 15.6±2.8 (37°C) to 39.7±10.9. Further, in patients either before or during xRT, when the lymphocytes were treated with HT (43.5°C) and combined with ex vivo irradiation, the MN yield ( Y) could be estimated by a linear equation Y= C+ αD. Our findings indicate that as measured by the MN production in cytokinesis-blocked lymphocytes, HT alone at 43.5°C induced DNA damage. Moreover, it enhanced the radiation-induced cytogenetic damage. Therefore, the application of HT may impair the T-cell function in cancer patients who are receiving radiotherapy.