Host: The Japan Radiation Research Society
The molecular mechanisms of heat-induced cellular responses are still unknown. For example, actual critical event in heat-induced cell killing has not yet been determined. Recently, we proposed that heat-induced cell killing might be associated with double strand breaks (DSBs) formation via protein denaturation for following results. (1) Using the neutral comet assay, we found that heat treatment induced DSBs in cellular DNA; (2) Heat treatment induced the formation of γH2AX foci, which is known to be quite sensitive and a specific indicator for the presence of DSBs; (3) An inflection point at 42.5oC, and the thermal activation energies above and below the inflection point were almost the same between cell killing and γH2AX foci formation according by Arrhenius plot analysis; (4) The cell-cycle-dependent pattern of heat-induced cell killing was the same as the cell cycle pattern of γH2AX foci formation; (5) Heat-induced gamma H2AX foci formation was suppressed in thermotolerance development; (6) DNA damage recognition proteins such as ATM phospho-serine 1981, DNA-PKcs phospho-threonine 2609, NBS1 phospho-serine 343, CHK2 phospho-threonine 68 and SMC1 phospho-serine 966 all co-localized with γH2AX after heat treatment.
In this workshop, we will discuss the possible mechanisms of heat-induced DSB formation. We expect that these approaches will constitute a breakthrough in hyperthermic biology and oncology.
