Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells

Heylmann, Daniel; Rödel, Franz; Kindler, Thomas; Kaina, Bernd

doi:10.1016/j.bbcan.2014.04.009

Cited by 168 publications

(174 citation statements)

References 58 publications

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“…One may speculate that DNA containing nicks or oxidative DNA damage is more efficient in forming NETs than unbroken (high-molecular weight) DNA and, therefore, DNA breaks due to failure in DNA repair are of advantage in this process, but this needs to be proven. It is striking that all cell types in the haematopoietic system are DSB repair competent [16], except monocytes [14] and, as shown here, terminally differentiated neutrophils in the peripheral blood. This raises the question as to the mechanism of downregulation of these DNA repair genes.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, monocyte-matured macrophages and DC re-express the relevant DNA repair proteins and therefore become resistant to genotoxins, including ionising radiation, chemical ROS and anticancer drugs [9, 13, 14]. Of note, T cells are repair competent similar to differentiated macrophages [16]. …”

Section: Introductionmentioning

confidence: 99%

“…Since granulocytes and monocytes arise from the same precursor in the bone marrow [16], we wondered whether granulocytes exhibit the same DNA repair defective phenotype as monocytes. Therefore, in this study, we analysed granulocytes (the majority in the population is neutrophils) and compared them with T cells as to their expression of DNA recognition and repair factors, their DNA repair capacity after genotoxic insult and induction of cell death.…”

Section: Introductionmentioning

confidence: 99%

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Compromised DNA Repair and Signalling in Human Granulocytes

Ponath¹,

Heylmann²,

Haak³

et al. 2018

J Innate Immun

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In previous studies, we showed impaired DNA repair in human monocytes. Here, we addressed the question of whether human neutrophilic granulocytes that arise from the same precursor as monocytes exhibit a similar phenotype and are impaired in repairing their DNA. We show that neutrophilic granulocytes isolated from peripheral blood display a lack of the same repair proteins that are missing in monocytes and do not show repair of their DNA when damaged by ionising radiation (IR) or chemical ROS. Contrary to T cells, we observed no decline in the number of single-strand breaks following γ-radiation. Also, granulocytes did not show γH2AX foci formation while T cells and peripheral blood lymphocytes (PBL) responded. In comparison to PBL, XRCC1, PARP-1 and ligase III were not expressed and there was also no discernible signal for key damage response proteins ATM, ATR and DNA-PK_CS as well as γH2AX in neutrophils. Time course and dose-response experiments confirmed the absence of H2AX phosphorylation after radiation treatment although an accumulation of double-strand breaks was detected in the neutral Comet assay. Overall, the data indicate that terminally differentiated neutrophilic granulocytes in the peripheral blood display strong downregulation of DNA repair and DNA damage response factors, which should be taken into account if studies with whole peripheral blood containing granulocytes are performed, causing a significant intra-experimental variation in the cellular repair capacity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Compromised DNA Repair and Signalling in Human Granulocytes

Ponath¹,

Heylmann²,

Haak³

et al. 2018

J Innate Immun

Self Cite

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“…These effects depend on the radiation dose and the organs irradiated (Amundson 2008;Rodel et al 2012). Also, different immune cells may respond differently to ionizing radiation (Heylmann et al 2014).…”

Section: Immunogenicity Of Ionizing Radiationmentioning

confidence: 99%

The melatonin immunomodulatory actions in radiotherapy

et al. 2017

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Radiotherapy has a key role in cancer treatment in more than half of patients with cancer. The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment. Immune system responses play a pivotal role in many of the early and late side effects of radiation. Moreover, immune cells have a significant role in tumor response to radiotherapy, such as angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs. These effects are mediated through various modulatory effects of melatonin in different levels of tissue reaction to ionizing radiation. The effects on the DNA repair system, antioxidant enzymes, immune cells, cytokines secretion, transcription factors, and protein kinases are most important. Moreover, anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy. Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results. It seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that may help to improve response of the tumor to radiotherapy. In this review, the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed.

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“…Sensitive cells include hematopoietic, germ (especially spermatogenic and follicular cells), intestinal nest cells (especially those of small intestine), and lymphocytes. 36 Compared with other radiation-sensitive cells, lymphocytes in peripheral blood are collected and detected much easily than the others. Thus, lymphocyte counts were used to estimate injury aer radiation exposure.…”

mentioning

confidence: 99%

SERS detection of radiation injury biomarkers in mouse serum

Xiao

Wang

et al. 2018

RSC Adv.

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In a large-scale radiological catastrophe, it is expected that hundreds and thousands of people could be exposed to radiation. A rapid method is required for triage of casualties to determine proper medical treatment. In this article, mice were exposed to different radiation doses and sera of mice were investigated by surface-enhanced Raman spectroscopy (SERS) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) after total body irradiation (TBI). The results of the present study indicated that differences have widened over time. The different radiation groups showed a slight overlap at 24 h and 72 h but were completely distinct at the 10th day after TBI. The SERS spectrum between the normal group and the irradiated group showed a significant difference at 24 hours. The same trend was depicted in scatting score plots. Significant differences in Raman peaks were found, such as 744 and 1495 cm À1 corresponding to riboflavin and 593 and 1204 cm À1 corresponding to Ltryptophan. The lack of riboflavin and L-tryptophan will influence metabolism levels. Above all, these results bear potential in the development of label-free and rapid tools for on-site detection and screening of irradiation injuries.

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Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells

Cited by 168 publications

References 58 publications

Compromised DNA Repair and Signalling in Human Granulocytes

Compromised DNA Repair and Signalling in Human Granulocytes

The melatonin immunomodulatory actions in radiotherapy

SERS detection of radiation injury biomarkers in mouse serum

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