Effect of ionizing radiation at low dose on transgenerational carcinogenesis by epigenetic regulation

Li, Lan; Kim, Jong-Hyun; Park, Heetae; Lee, Jae‐Hoon; Park, Min-Koo; Lee, Jiwon; Lee, Jeungchan; Lee, Min-Jae

doi:10.5625/lar.2017.33.2.92

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…DNA methylation status, particularly its repetitive elements (which represent the largest methylated body of coding noncoding sequences in the genome), is a potential biomarker to study radiation-induced epigenetic alterations [362]. Interestingly, it has been demonstrated that the levels of expression in different tumor suppressor genes have different radiation threshold levels [363]. The study demonstrated the hypermethylation of the tumor suppressor gene SOCS1 in the group receiving 30 rad.…”

Section: Epigeneticsmentioning

confidence: 93%

“…Moreover, genes related to the DNA damage response pathway (GSTP1, ATM, DGKA, PARP1, and SIRT6) were epigenetically inactivated in the groups receiving a carcinogen. Regarding proto-oncogene c-Myc, in the group with a low dose of infrared radiation (IR) (10 rad), DNA hypermethylation was detected [363], thus suggesting that, when considering radiation-induced epigenetic changes, organ-specific and radiation dose-dependent effects must be taken into account.…”

Section: Epigeneticsmentioning

confidence: 99%

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Radioprotection and Radiomitigation: From the Bench to Clinical Practice

et al. 2020

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The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by the FDA as a radiation countermeasure for acute radiation syndrome (ARS). All FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring granulocyte colony-stimulating factor, G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant granulocyte macrophage colony-stimulating factor, GM-CSF) are classified as radiomitigators. No radioprotector that can be administered prior to exposure has been approved for ARS. This differentiates radioprotectors (reduce direct damage caused by radiation) and radiomitigators (minimize toxicity even after radiation has been delivered). Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed. Assays to evaluate the biological effects of ionizing radiations are also analyzed.

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Section: Epigeneticsmentioning

confidence: 93%

Section: Epigeneticsmentioning

confidence: 99%

Radioprotection and Radiomitigation: From the Bench to Clinical Practice

et al. 2020

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“…Epigenetic changes include DNA methylation, histone acetylation, and miRNA-regulated gene expression 127,128 . Epigenetic alterations have been found to contribute to the pathogenesis of radiation-induced carcinogenesis 129 by the reactivation of oncogenes and the silencing of tumor suppressor genes 130 . These events can result in genomic instability and consequent carcinogenesis in many models 131–134 .…”

Section: Embryonic and Fetal Ddr And Sensitivity To Irmentioning

confidence: 99%

Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity

Fabbrizi

Warshowsky

Zobel

et al. 2018

Cell Death Discovery

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Ionizing radiation (IR) therapy is a major cancer treatment modality and an indispensable auxiliary treatment for primary and metastatic cancers, but invariably results in debilitating organ dysfunctions. IR-induced depletion of neural stem/progenitor cells in the subgranular zone of the dentate gyrus in the hippocampus where neurogenesis occurs is considered largely responsible for deficiencies such as learning, memory, and spatial information processing in patients subjected to cranial irradiation. Similarly, IR therapy-induced intestinal injuries such as diarrhea and malabsorption are common side effects in patients with gastrointestinal tumors and are believed to be caused by intestinal stem cell drop out. Hematopoietic stem cell transplantation is currently used to reinstate blood production in leukemia patients and pre-clinical treatments show promising results in other organs such as the skin and kidney, but ethical issues and logistic problems make this route difficult to follow. An alternative way to restore the injured tissue is to preserve the stem cell pool located in that specific tissue/organ niche, but stem cell response to ionizing radiation is inadequately understood at the molecular mechanistic level. Although embryonic and fetal hypersensity to IR has been very well known for many decades, research on embryonic stem cell models in culture concerning molecular mechanisms have been largely inconclusive and often in contradiction of the in vivo observations. This review will summarize the latest discoveries on stem cell radiosensitivity, highlighting the possible molecular and epigenetic mechanism(s) involved in DNA damage response and programmed cell death after ionizing radiation therapy specific to normal stem cells. Finally, we will analyze the possible contribution of stem cell-specific chromatin’s epigenetic constitution in promoting normal stem cell radiosensitivity.

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RIBE from Multiple Irradiation and the Protective Effects of Astragalus Polysaccharides on Methylation and Cancer-associated Proteins in BMSCs

Zhang,

Zhou,

Zhang

et al. 2024

Pharmacognosy Magazine

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Background: Ionizing radiation can induce bystander effects (RIBE), and astragalus polysaccharides (APS) have a protective effect against RIBE. It has been proved that RIBE occurred and APS played the inhibitory effects on the RIBE when radiation was carried out only one time. However, whether RIBE happened by multiple irradiations and the effects of APS on the RIBE are unclear. This study aimed to investigate whether APS suppress RIBE damage induced by multiple irradiations. Materials and Methods: A549 cells were irradiated with 2 Gy X-rays to obtain a conditioned medium. Bone mesenchymal stem cells (BMSCs) was incubated with the conditioned medium 5 times every 3 days or APS. Cell proliferation was detected by CCK-8 and colony formation assay, and genomic instability and DNA damages were detected by the micronucleus and immunofluorescence assay. The protein associated with methylation and cancer-associated proteins in BMSCs were detected by western blot. Results: After five stimulations with a conditioned medium, the proliferative capacity of BMSCs decreased; APS pre-intervention promoted the proliferation of BMSCs. And conditional medium intervention increased the micronucleus rate and a number of 53BP1 foci; APS pre-intervention reduced the micronucleus rate and number of 53BP1 foci. In addition, the conditional medium intervention reduced the expression of methylation-related proteins and increased the expression of cancer-related proteins, while APS pre-intervention reversed this trend. Conclusion: Irradiated A549 conditioned medium can induce RIBE of BMSCs, which might be related to methylation and cancer-associated proteins and APS may block RIBE by multiple irradiations in BMSCs.

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Effect of ionizing radiation at low dose on transgenerational carcinogenesis by epigenetic regulation

Cited by 3 publications

References 20 publications

Radioprotection and Radiomitigation: From the Bench to Clinical Practice

Radioprotection and Radiomitigation: From the Bench to Clinical Practice

Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity

RIBE from Multiple Irradiation and the Protective Effects of Astragalus Polysaccharides on Methylation and Cancer-associated Proteins in BMSCs

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