Fractionated exposure to low doses of ionizing radiation results in accumulation of DNA damage in mouse spleen tissue and activation of apoptosis in a p53/Atm-independent manner

Koturbash, Igor; Merrifield, Matt; Kovalchuk, Olga

doi:10.1080/09553002.2017.1231943

Cited by 11 publications

(7 citation statements)

References 38 publications

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“…This location dependence suggests that potential lymphocyte-sparing effects of PBT may be most pertinent for limiting integral doses to organs adjacent to the lower esophagus and gastroesophageal junction, such as the spleen. The spleen, in particular, which is a large lymphocyte reservoir, could be more likely to receive integral doses [22, 23]. In addition, circulating lymphocytes in other organs, such as the lung, liver, and stomach, could also be at risk [24, 25].…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte-Sparing Effect of Proton Therapy in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

Fang

Shiraishi

Verma

et al. 2017

International Journal of Particle Therapy

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Purpose To assess whether radiation treatment modality with proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) is associated with lymphopenia in patients treated with definitive chemoradiation for esophageal cancer. Methods and Materials Patients with esophageal cancer treated with bimodality therapy (n = 448) between 2004 and 2016 were retrospectively reviewed. Patients treated with PBT were matched by propensity score with those treated with IMRT, based on key patient and disease factors, and stratified by clinical disease stage. Patients who developed early, distant metastatic disease within 1 month of completing radiation were excluded. Univariable and multivariable logistic regression were used to identify variables associated with increased risk of grade 4 lymphopenia. Multivariable Cox proportional hazards regression was used to assess factors associated with overall survival, disease-free survival, and locoregional relapse-free survival. Results Patients who had IMRT and PBT matched by propensity score (n = 220) were not different with respect to age, sex, stage, performance status, tumor location, histology, tumor target volume, or induction chemotherapy. Treatment with IMRT, compared with PBT (odds ratio [OR], 2.13; 95% confidence interval [95% CI], 1.19–3.81; P = .01), increased age (OR, 1.039/y increase; 95% CI, 1.003–1.076; P = .03), and greater planning target volume (OR, 3.47 per 1-unit increase in log (planning target volume); 95% CI, 1.67–7.21; P < .001), was associated with increased risk of grade 4 lymphopenia. Radiation modality was associated with lymphocyte reduction in patients with tumors in the lower esophagus (P = .005) but not for those with tumors in the upper or middle esophagus (P = 0.32). Conclusions In patients with esophageal cancer treated with definitive chemoradiation, PBT reduces the risk of severe, treatment-related lymphopenia, particularly in tumors of the lower esophagus.

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Section: Discussionmentioning

confidence: 99%

Lymphocyte-Sparing Effect of Proton Therapy in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

Fang

Shiraishi

Verma

et al. 2017

International Journal of Particle Therapy

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“…In recent years, fractionated radiation delivery is most often studied over short periods of time and the animals are sacrificed soon after exposure. For example, apoptosis and DNA damage were studied in spleen cells of mice exposed to 0.1 to 0.5 Gy of x-rays over one to 5 days, sacrificed 6 or 24 h after final exposure (Koturbash et al 2017). However, in the period before year 2000 numerous fractionated radiation studies were done and archival data from this work are still often used for cancer incidence analyses.…”

Section: Extended Studies Of Low Linear Energy Transfer (Let) Irradiated Wild Type Animalsmentioning

confidence: 99%

“…Therefore, it is possible that immune system activation caused by low dose radiation exposures could be an added factor of interest in evaluation of low dose radiation effects. Some of the short term studies also evaluated DNA damage and apoptosis in spleen cells of wild type mice (Koturbash et al 2017). In this work, 60-day old wild type C57BL/6 male mice were sacrificed at 6 or 24 h after exposure to the last fraction of whole body x-ray irradiation at a dose rate of 50 mGy/s.…”

Section: Research Focused On Dna Damage In Animals Exposed To Low Dose or Low Dose Rate Low Let Radiationmentioning

confidence: 99%

Effects of low dose and low dose rate low linear energy transfer radiation on animals – review of recent studies relevant for carcinogenesis

Paunesku

Stevanović

Popović

et al. 2021

International Journal of Radiation Biology

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Purpose: Carcinogenic effects of radiation are often assumed to be universally understood, more often than, for example, carcinogenic effects of many different chemicals. This in turn leads to an assumption that any dose of radiation, delivered at any dose rate, poses a serious health challenge. This remains an issue of dispute and low dose radiation research is focused on understanding whether these exposures contribute to cancer incidence. This review is focused on the low linear energy transfer (low LET) radiation exposures for which the data is the most abundant in recent years. Materials and methods: Review of the literature between 2008 and today, highlighting some of the most diverse studies in low dose research. Results: Low dose and low dose rate, low LET ionizing radiation animal studies suggest that the effects of exposure very much depend on animal genotype and health status. Conclusions: Only the integration of all of the data from different models and studies will lead to a fuller understanding of low dose radiation effects. Therefore, we hope to see an increase in international archival efforts and exchange of raw data information opening the possibilities for new types of meta analyses.

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“…GO(Gene Ontology) [33] 和KEGG (Kyoto Encyclopedia of Genes and Genomes Pathways) [34] [37] , 在0.5和2 Gy剂量 12 C 6+ 辐照后表达量变化均在1倍以下. ATM [38] , PARP3 [39,40] 和LIG4 [41,42]…”

Section: 开发为辐射诱导癌发生的干预药物此外巯基化合物mentioning

confidence: 99%

Identification and prediction of molecular targets related to space radiation protection based on associated networks

et al. 2019

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Fractionated exposure to low doses of ionizing radiation results in accumulation of DNA damage in mouse spleen tissue and activation of apoptosis in a p53/Atm-independent manner

Cited by 11 publications

References 38 publications

Lymphocyte-Sparing Effect of Proton Therapy in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

Lymphocyte-Sparing Effect of Proton Therapy in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

Effects of low dose and low dose rate low linear energy transfer radiation on animals – review of recent studies relevant for carcinogenesis

Identification and prediction of molecular targets related to space radiation protection based on associated networks

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