Intracellular distribution of hsp70 during long duration moderate hyperthermia

Hyperthermia causes cell killing and is also an effective radiosensitizer. In recent years, the protocol of long duration moderate hyperthermia (LDMH) has been used to treat cancer patients in the clinic. However, the results of many studies indicate that some tumour cells may reveal the capability to express chronic thermotolerance, a factor of potentially critical impact in the efficacy of clinical hyperthermia. Previously it has been reported that two out of five human cell lines studied were able to proliferate at 41.1 degrees C. In the present study, the intracellular distribution of hsp70 during LDMH was measured as a potential marker for chronic thermotolerance with continued cell proliferation. In all cell lines studied, hsp70 became localized in the nucleus immediately after the cells were shifted from 37 degrees C to 41.1 degrees C. However, in the two cell lines which recovered and continued to proliferate, NSY42129 and HT29, hsp70 was delocalized from the nucleus within 4 h. Conversely, in the cell lines for which 41.1 degrees C was lethal, hsp70 did not delocalize from the nucleus but rather became localized in the nucleolar regions. Neither the NSY42129 cells nor the HT29 cells showed any preferential nucleolar punctate staining. Thus, it appears that the pattern of hsp70 nuclear localization and delocalization is related to the cells' ability to survive moderate heat shocks.