Heat exposure enhances radiosensitivity by depressing DNA-PK kinase activity during double strand break repair. (March 2014)

• Record Type: Journal Article
• Authors: Ihara, Makoto; Takeshita, Satoshi; Okaichi, Kumio; Okumura, Yutaka; Ohnishi, Takeo
• Is Part Of: International journal of hyperthermia. Volume 30:Number 2(2014)
• Page Start: 102
• Page End: 109
• Publication Date: 2014-03
• Subjects: Thermotherapy -- Periodicals; 615.832
• DOI: 10.3109/02656736.2014.887793
• Languages: English
• ISSNs: 0265-6736

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: From the role of double strand DNA dependent protein kinase (DNA-PKcs) activity of non-homologous end joining (NHEJ) repair for DNA double strand breaks (DSBs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in X-ray irradiated cells. <italic>Materials and methods</italic>: <italic>DNA-PKcs</italic> deficient mouse, Chinese hamster and human cultured cells were compared to the parental wild-type cells. The radiosensitivities, the number of DSBs and DNA-PKcs activities after heat-treatment were measured. <italic>Results</italic>: Both <italic>DNA-PKcs</italic> deficient cells and the wild-type cells showed increased radiosensitivities after heat-treatment. The wild-type cells have two repair processes; fast repair and slow repair. In contrast, <italic>DNA-PKcs</italic> deficient cells have only the slow repair process. The fast repair component apparently disappeared by heat-treatment in the wild-type cells. In both cell types, additional heat exposure enhanced radiosensitivities. Although DNA-PKcs activity was depressed by heat, the inactivated DNA-PKcs activity recovered during an incubation at 37 °C. DSB repair efficiency was dependent on the reactivation of DNA-PKcs activity. <italic>Conclusion</italic>: It was suggested that NHEJ is the major process used to repair X-ray-induced DSBs and utilises DNA-PKcs activity, but homologous recombination repair provides additional secondary levels of DSB repair. The thermo-sensitisation in X-ray-irradiated cells depends on the inhibition of NHEJ repair through the depression of DNA-PKcs activities.</p> </abstract>