title: Heat-induced intranuclear protein aggregation and thermal radiosensitization.
abstract: In the current study, the hypothesis that thermal radiosensitization is (indirectly) caused by heat-induced denaturation and aggregation of nuclear proteins is further investigated. Thermotolerant rodent cells showed a reduced intranuclear protein aggregation as compared with non-tolerant cells immediately after a heat treatment. This was reflected in the extent of radiosensitization when the cells were X-irradiated immediately after a heat treatment. When heat and radiation were separated in time, a faster disaggregation was found in thermotolerant cells, which was paralleled by a more rapid decline of radiosensitization. Cells transfected with hsp72 showed protection against heat-induced nuclear protein aggregation and reduced thermal radiosensitization. Transfection with hsp27 resulted in an accelerated nuclear protein disaggregation and accelerated decline of thermal radiosensitization. Despite a significant overall correlation between TER and nuclear protein aggregation, the slopes of the correlation curves for the individual cell lines deviated significantly. Yet, the experiments support the hypothesis that radiosensitization is primarily caused by inhibition of DNA repair as a result of the presence of denatured and aggregated proteins in the cell nucleus. Expression of hsps (e.g. in thermotolerant cells), by affecting nuclear protein aggregation, can have an impact on thermal radiosensitization.
authors.affiliation: Department of Radiobiology, University of Groningen, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Stege
authors.forename: H H
authors.initials: HH
authors.lastname: Kampinga
authors.forename: A W
authors.initials: AW
authors.lastname: Konings
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006358:Hot Temperature; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry*; D011489:Protein Denaturation; D011836:Radiation Tolerance; D051381:Rats; D014965:X-Rays
chemical_list: D009687:Nuclear Proteins