The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation

Ćmielová, Jana; Havelek, Radim; Köhlerová, Renata; Soukup, Tomáš; Brůčková, Lenka; Suchánek, J; Vávrová, Jiřina; Mokrý, Jaroslav; Řezáčová, Martina

doi:10.3109/09553002.2013.775530

Cited by 14 publications

(11 citation statements)

References 37 publications

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“…Considering the important role of ATM, an even higher reduction in IR-induced gene activation than the average ca. 50% reduction upon ATM inhibition could perhaps have been expected, based on studies using p21 CIP1/WAF1 protein levels as endpoint in other cell systems [37,38]. No other studies using ATM or DNA-PK inhibition were found assaying DDR gene expression at a similar time point; perhaps the high radiosensitivity of lymphocytes merely overloads the potential of the ATM inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

Cheng

Brzozowska

Lisowska

et al. 2019

Cancers

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Accumulating evidence suggests a synergistic effect in cells simultaneously exposed to different types of clustered and dispersed DNA damage. We aimed to analyse the effect of mixed beams of alpha particles and X-rays (1:1 dose of each) on DNA damage response genes in human peripheral blood lymphocytes isolated from four donors. Two donors were compared upon inhibition of ATM or DNA-PK and at different sampling times. qPCR was used to measure mRNA levels of FDXR, GADD45A, BBC3, MDM2, CDKN1A, and XPC 24 h following exposure. Generally, alpha particles and mixed beams were stronger inducers of gene expression compared to X-rays, displaying saturated versus linear dose-response curves, respectively. Three out of four donors responded synergistically to mixed beams. When two donors were sampled again one year later, the former additive effect in one donor was now synergistic and no significant difference in intrinsic radiosensitivity was displayed, as determined by gamma-radiation-induced micronuclei. ATM, but not DNA-PK inhibition, reduced the radiation-induced gene expression, but differently for alpha radiation between the two donors. In conclusion, synergy was present for all donors, but the results suggest individual variability in the response to mixed beams, most likely due to lifestyle changes.

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Section: Discussionmentioning

confidence: 99%

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

Cheng

Brzozowska

Lisowska

et al. 2019

Cancers

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“…The data on radiosensitivity of hMSC are still limited; just a few published reports provide some information regarding the survival/cell fate of irradiated hMSC derived from different body locations [42–46]. In general, hMSCs were found to be relatively resistant to IR exposures [42,47,48].…”

Section: Human Stem Cell Radiosensitivitymentioning

confidence: 99%

“…Even relatively low doses of IR (0.5 Gy) elicited p53 induction in hMSC cultures [47]. Posttranslational modifications of p53 on ser 15, Chk1 on ser 345 and Chk2 on thr 68 were found to be strongly dependent on ATM function [46]. Expression of Hdm2 correlated well with that of p53; Hdm2 is activated by phosphorylation at serine 166 in hMSCs post-IR [51].…”

Section: Effects Of Ionizing Radiation Exposures On Dna Damage Resmentioning

confidence: 99%

Lessons Learned about Human Stem Cell Responses to Ionizing Radiation Exposures: A Long Road Still Ahead of Us

Sokolov

Neumann

2013

IJMS

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Human stem cells (hSC) possess several distinct characteristics that set them apart from other cell types. First, hSC are self-renewing, capable of undergoing both asymmetric and symmetric cell divisions. Second, these cells can be coaxed to differentiate into various specialized cell types and, as such, hold great promise for regenerative medicine. Recent progresses in hSC biology fostered the characterization of the responses of hSC to genotoxic stresses, including ionizing radiation (IR). Here, we examine how different types of hSC respond to IR, with a special emphasis on their radiosensitivity, cell cycle, signaling networks, DNA damage response (DDR) and DNA repair. We show that human embryonic stem cells (hESCs) possess unique characteristics in how they react to IR that clearly distinguish these cells from all adult hSC studied thus far. On the other hand, a manifestation of radiation injuries/toxicity in human bodies may depend to a large extent on hSC populating corresponding tissues, such as human mesenchymal stem cells (hMSC), human hematopoietic stem cells (hHSC), neural hSC, intestine hSC, etc. We discuss here that hSC responses to IR differ notably across many types of hSC which may represent the distinct roles these cells play in development, regeneration and/or maintenance of homeostasis.

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“…DNA damage was measured using both alkaline and neutral versions of the comet assay (4). The alkaline version suitable for SSB detection has been described previously (5, 6).…”

Section: Methodsmentioning

confidence: 99%

Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest

Hazuková

Řezáčová

Köhlerová³

et al. 2017

Anatol J Cardiol

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Objective:This study aimed to investigate whether out-of-hospital cardiac arrest (OHCA) may induce severe DNA damage measured using comet assay in successfully resuscitated humans and to evaluate a short-term prognostic role.Methods:In this prospective, controlled, blinded study (1/2013–1/2014), 41 patients (age, 63±14 years) successfully resuscitated from non-traumatic OHCA and 10 healthy controls (age, 53±17 years) were enrolled. DNA damage [double-strand breaks (DSBs) and single-strand breaks (SSBs)] was measured using comet assay in peripheral lymphocytes sampled at admission. Clinical data were recorded (according to Utstein style). A good short-term prognosis was defined as survival for 30 days.Results:Among the patients, there were 71% (29/41) short-term survivors. After OHCA, DNA damage (DSBs and SSBs) was higher (11.0±7.6% and 0.79±2.41% in tail) among patients than among controls (1.96±1.63% and 0.02±0.03% in tail), and it was more apparent for DSBs (p<0.001 and p=0.085). There was no difference in the DNA damage between patients with cardiac and non-cardiac etiology, or between survivors and nonsurvivors. Among Utstein style parameters, ventricular fibrillation, asystole, and early electrical defibrillation influenced DSB; none of the factors influenced SSBs. Factors influencing survival were SSBs, ventricular fibrillation, length of cardiopulmonary resuscitation by professionals ≤15 min, cardiogenic shock, and postanoxic encephalopathy. In contrast to DSBs [area under the curve (AUC)=0.520], SSBs seem to have a potential in prognostication (AUC=0.639).Conclusion:This study for the first time demonstrates revelation of DNA damage using comet assay in patients successfully resuscitated from OHCA. Whether DNA damage measured using comet assay may be a prognostic marker remains unknown, although our data may encourage some suggestions.

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The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation

Cited by 14 publications

References 37 publications

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

Lessons Learned about Human Stem Cell Responses to Ionizing Radiation Exposures: A Long Road Still Ahead of Us

Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest

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