Effect of an ATM kinase inhibitor on thermo- and/or radio-sensitization in non-proliferating normal human fibroblasts and osteosarcoma cells

This aim of the work described here was to determine the effect of an ataxia-telangiectasia mutated protein (ATM) kinase inhibitor on thermo- and/or radio-sensitivity in normal human fibroblasts cells and in osteosarcoma cells in the plateau or confluent phase of cell growth. Cell survival and chromosome aberrations were observed when cells were exposed to a heat shock at 45 deg C and/or γ-rays in the presence or absence of an ATM kinase inhibitor. Cell survival was measured with colony formation assays. Chromosome aberrations were observed using chemically induced premature chromosome condensation and fluorescence in situ hybridization. Cellular radiosensitivity was enhanced in both cell lines by a heat shock treatment at 45 deg C. Adding an ATM kinase inhibitor amplified this effect. Furthermore, thermosensitivity in both cell lines at 45 deg C was enhanced by treatment with an ATM kinase inhibitor. Heat shock treatments at 45 deg C enhanced the frequency of chromosome aberrations induced by γ-irradiation in both cell lines; in the presence of an ATM kinase inhibitor, the frequency of chromosome aberrations was enhanced. Thus, ATM kinase inhibitors increased the number of heat-induced aberrations. These results were observed in both, normal human fibroblasts cells and osteosarcoma cells. ATM kinase inhibitors can contribute to heat-induced cell killing and to heat-induced cellular chromosome aberration frequencies in the plateau or confluent phase of cell growth. (author)