Hyperthermia enhances thermal-neutron-induced cell death of human glioblastoma cell lines at low concentrations of 10B.

OBJECTIVE

To examine the ability of pre- vs. post-irradiation hyperthermia to enhance the effectiveness of thermal neutrons to kill human glioblastoma cells.

METHODS

Human glioblastoma cell lines, T98G, A7, A172, and U 87MG, were exposed to thermal neutrons from the Kyoto University Research (KUR) reactor or to 60Co gamma-rays. Hyperthermia was tested before and after irradiation of T98G (44 degrees C, 15 min) and A7 cells (44 degrees C, 40 min), and with different concentrations (0-30 ppm) of 10B-boric acid. The biological end point of all experiments was cell survival measured by a colony formation assay.

RESULTS

The relative biological effectiveness (RBE) values of thermal neutrons for these cell lines compared with 60Co gamma-rays were 1.8-2.0 at their D(0) values. When T98G and A7 cells were heated after thermal neutron irradiation, there was a synergistic effect at low 10B concentrations (up to 5 ppm for T98G and up to 10 ppm for A7 cells). With high concentrations of boron (10-30 ppm for T98G and 20-30 ppm for A7 cells), hyperthermia and neutron irradiation interact additively rather than synergistically. There was no enhancement when cells were heated before thermal neutron irradiation. These results suggest that the radiosensitizing effect of hyperthermia may be attributed to partial inhibition of the repair of the potentially lethal damage caused by neutron irradiation.