Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining

Bergs, Judith; Krawczyk, Przemek M.; Borovski, Tijana; Cate, Rosemarie ten; Rodermond, Hans M.; Stap, Jan; Medema, Jan Paul; Haveman, J.; Essers, Jeroen; Bree, Chris van; Stalpers, Lukas J.A.; Kanaar, Roland; Aten, Jacob A.; Franken, Nicolaas A.P.

doi:10.1016/j.dnarep.2012.10.008

Cited by 45 publications

(39 citation statements)

References 60 publications

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“…As reviewed by Bergs et al (2007), it has been demonstrated by several studies that all three agents applied together yield a clear enhancement of effects compared to single-or bi-modality treatments. Hyperthermia increases radiation sensitivity by inhibiting homologous recombination repair and in addition cisplatin increases the radiation sensitivity by disrupting endjoining repair and base excision repair (Bergs et al 2006(Bergs et al , 2013Oei et al 2015). This explains the increased effect for the tri-modality strategy.…”

Section: Discussionmentioning

confidence: 78%

“…The interaction of hyperthermia with ionizing radiation probably results from inhibition of repair of radiation-induced DNA damage by hyperthermia which was recently described Bergs et al 2013;Oei et al 2015). It was demonstrated that hyperthermia treatment combined with ionizing radiation led to inhibition of the cellular capacity to repair PLD (Oei et al 2015).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Franken

Kok

Crezee

et al. 2016

International Journal of Radiation Biology

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Purpose: To evaluate the enhancement effect of two combined radiation-sensitizing agents in mammalian cells at small doses as compared to large doses using the linear-quadratic (LQ) mathematical model. Methods and materials: Data on clonogenic assays concerning the radio-enhancement effects of combined halogenated pyrimidines and hyperthermia or combined cisplatin and hyperthermia, as published in earlier reports, were analyzed according to the LQ-formula:). Effects of sensitizing agents on the linear parameter a and the quadratic parameter b are compared in order to evaluate differences depending on the applied dose, the possible relations to mechanisms of radiation sensitization and to derive suggestions for applications. Results: The values of the linear parameter a, which determines the effectiveness at low doses, are for all cell lines and all conditions more increased than the values of the parameter b which has a higher contribution at larger radiation doses. The combination of hyperthermia with halogenated pyrimidines to radiation as well as the combination of hyperthermia and cisplatin to radiation significantly increases the value of the linear parameter a, as compared to radiation alone or radiation combined with a single agent. Conclusions:The radiation enhancement factors of the values of linear and quadratic parameters demonstrate that the sensitizing agents have a larger effect on the linear parameter which is dominant at low radiation doses as is used in fractionated-radiation treatment in the clinic. Moreover, the effect is even further increased when two radiation sensitizers are used. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Franken

Kok

Crezee

et al. 2016

International Journal of Radiation Biology

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“…Previous work suggested modest inhibitory effects of nucleoside analogue on global DNA repair (4) and more recent reports suggest that nucleoside analogues interfere with proper execution of HRR (45). Recent advances in our understanding of DSB repair and the discovery of alternative pathways of end-joining with backup function, generate an entirely new intellectual framework for the mechanistic analysis of radiosensitizing treatments, as shown for hyperthermia (46). Indeed, radiosensitization may be caused not only by selective inhibition of a specific DSB repair pathway, but also by a shift in the balance between them.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Homologous Recombination and Promotion of Mutagenic Repair of DNA Double-Strand Breaks Underpins Arabinoside–Nucleoside Analogue Radiosensitization

Magin

Papaioannou

Saha

et al. 2015

Molecular Cancer Therapeutics

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In concurrent chemoradiotherapy, drugs are used to sensitize tumors to ionizing radiation. Although a spectrum of indications for simultaneous treatment with drugs and radiation has been defined, the molecular mechanisms underpinning tumor radiosensitization remain incompletely characterized for several such combinations. Here, we investigate the mechanisms of radiosensitization by the arabinoside nucleoside analogue 9-b-D-arabinofuranosyladenine (araA) placing particular emphasis on the repair of DNA double-strand breaks (DSB), and compare the results to those obtained with fludarabine

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“…HR is a high fidelity type repair and takes place only in actively cycling cells (Povirk, 2006). In contrast, NHEJ is not cell cycle phase restricted and represents a more error-prone mechanism (Bergs et al, 2013). The misrepaired DNA could lead to chromosomal deletions, insertions or translocations (Falk et al, 2010), and subsequently instability and malignant transformation.…”

Section: Discussionmentioning

confidence: 98%

Significant accumulation of persistent organic pollutants and dysregulation in multiple DNA damage repair pathways in the electronic-waste-exposed populations

Jing

Wang

et al. 2015

Environmental Research

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Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining

Cited by 45 publications

References 60 publications

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Inhibition of Homologous Recombination and Promotion of Mutagenic Repair of DNA Double-Strand Breaks Underpins Arabinoside–Nucleoside Analogue Radiosensitization

Significant accumulation of persistent organic pollutants and dysregulation in multiple DNA damage repair pathways in the electronic-waste-exposed populations

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