scholarly journals Stochastic Thresholds: A Novel Explanation of Nonlinear Dose-Response Relationships for Stochastic Radiobiological Effects

Dose-Response ◽  
2005 ◽  
Vol 3 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
Bobby R. Scott
Keyword(s):  
Dna Repair ◽  
Transition Zone ◽  
Dose Response ◽  
Low Dose ◽  
Nuclear Dna ◽  
Complete Inhibition ◽  
Photon Radiation ◽  
High Fidelity ◽  
Stochastic Effects ◽  
Radiation Induced

New research data for low-dose, low- linear energy transfer (LET) radiation-induced, stochastic effects (mutations and neoplastic transformations) are modeled using the recently published NEOTRANS3 model. The model incorporates a protective, stochastic threshold (StoThresh) at low doses for activating cooperative protective processes considered to include presumptive p53-dependent, high-fidelity repair of nuclear DNA damage in competition with presumptive p53-dependent apoptosis and a novel presumptive p53-independent protective apoptosis mediated (PAM) process which selectively removes genomically compromised cells (mutants, neoplastic transformants, micronucleated cells, etc.). The protective StoThresh are considered to fall in a relatively narrow low-dose zone (Transition Zone A). Below Transition Zone A is the ultra-low-dose region where it is assumed that only low-fidelity DNA repair is activated along with presumably apoptosis. For this zone there is evidence for an increase in mutations with increases in dose. Just above Transition Zone A, a Zone of Maximal Protection (suppression of stochastic effects) arises and is attributed to maximal cooperation of high-fidelity, DNA repair/apoptosis and the PAM process. The width of the Zone of Maximal Protection depends on low-LET radiation dose rate and appears to depend on photon radiation energy. Just above the Zone of Maximal Protection is Transition Zone B, where deleterious StoThresh for preventing the PAM process fall. Just above Transition Zone B is a zone of moderate doses where complete inhibition of the PAM process appears to occur. However, for both Transition Zone B and the zone of complete inhibition of the PAM process, high-fidelity DNA repair/apoptosis are presumed to still operate. The indicated protective and deleterious StoThresh lead to nonlinear, hormetic-type dose-response relationships for low-LET radiation-induced mutations, neoplastic transformation and, presumably, also for cancer.

scholarly journals Mechanistic Basis for Nonlinear Dose-Response Relationships for Low-Dose Radiation-Induced Stochastic Effects

2003 ◽  
Vol 1 (1) ◽  
pp. 154014203908444 ◽  
Author(s):  
Bobby R. Scott ◽  
Dale M. Walker ◽  
Yohannes Tesfaigzi ◽  
Helmut Schöllnberger ◽  
Vernon Walker
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Neoplastic Transformation ◽  
Radioactive Material ◽  
Low Dose Radiation ◽  
Stochastic Effects ◽  
Cancer Induction ◽  
Radiation Induced ◽  
Dose Radiation ◽  
Lnt Model

The linear nonthreshold (LNT) model plays a central role in low-dose radiation risk assessment for humans. With the LNT model, any radiation exposure is assumed to increase one's risk of cancer. Based on the LNT model, others have predicted tens of thousands of deaths related to environmental exposure to radioactive material from nuclear accidents ( e.g., Chernobyl) and fallout from nuclear weapons testing. Here, we introduce a mechanism-based model for low-dose, radiation-induced, stochastic effects (genomic instability, apoptosis, mutations, neoplastic transformation) that leads to a LNT relationship between the risk for neoplastic transformation and dose only in special cases. It is shown that nonlinear dose-response relationships for risk of stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected based on known biological mechanisms. Further, for low-dose, low-dose rate, low-LET radiation, large thresholds may exist for cancer induction. We summarize previously published data demonstrating large thresholds for cancer induction. We also provide evidence for low-dose-radiation-induced, protection (assumed via apoptosis) from neoplastic transformation. We speculate based on work of others ( Chung 2002 ) that such protection may also be induced to operate on existing cancer cells and may be amplified by apoptosis-inducing agents such as dietary isothiocyanates.

The Progress of ICRP New Recommendations

2010 ◽  
Author(s):  
Aiguo Shang ◽  
Changjie Lu ◽  
Jin Qin
Keyword(s):  
Comparative Analysis ◽  
Dose Rate ◽  
Low Dose ◽  
System Analysis ◽  
Weighting Factor ◽  
Radiological Protection ◽  
Stochastic Effects ◽  
Risk Coefficient ◽  
Low Dose Rate ◽  
Radiation Induced

In order to probe into the usage of the Recommendations of the ICRP, through comparative analysis of low-dose-rate radiation-induced stochastic effects of a nominal risk coefficient, radiation weighting factor, tissue weighting factor as well as the the implementation of changes on the radiological protection system, analysis of the international on Radiological Protection fundamental recommendations of the Committee on the latest changes in radiological protection and development, and that these changes can not affect the existing radiation protection of China’s basic policy and standards.

scholarly journals Distinct vascular genomic response of proton and gamma radiation

2018 ◽  
Author(s):  
Ricciotti Emanuela ◽  
Dimitra Sarantopoulou ◽  
Gregory R. Grant ◽  
Jenine K. Sanzari ◽  
Gabriel S. Krigsfeld ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Dose Response ◽  
Photon Radiation ◽  
Radiation Response ◽  
Whole Body ◽  
Proton Radiation ◽  
Vascular Effects ◽  
Radiation Induced ◽  
Total Body ◽  
Genomic Response

AbstractPurpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge.Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 - 200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results.While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes;q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation;p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships.Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

scholarly journals Low Dose Ionising Radiation-Induced Hormesis: Therapeutic Implications to Human Health

2021 ◽  
Vol 11 (19) ◽  
pp. 8909
Author(s):  
Yeh Siang Lau ◽  
Ming Tsuey Chew ◽  
Amal Alqahtani ◽  
Bleddyn Jones ◽  
Mark A. Hill ◽  
...  
Keyword(s):  
Human Health ◽  
Dose Response ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Ionising Radiation ◽  
High Dose ◽  
Therapeutic Implications ◽  
Therapeutic Benefits ◽  
Biological Phenomena ◽  
Radiation Induced

The concept of radiation-induced hormesis, whereby a low dose is beneficial and a high dose is detrimental, has been gaining attention in the fields of molecular biology, environmental toxicology and radiation biology. There is a growing body of literature that recognises the importance of hormetic dose response not only in the radiation field, but also with molecular agents. However, there is continuing debate on the magnitude and mechanism of radiation hormetic dose response, which could make further contributions, as a research tool, to science and perhaps eventually to public health due to potential therapeutic benefits for society. The biological phenomena of low dose ionising radiation (LDIR) includes bystander effects, adaptive response, hypersensitivity, radioresistance and genomic instability. In this review, the beneficial and the detrimental effects of LDIR-induced hormesis are explored, together with an overview of its underlying cellular and molecular mechanisms that may potentially provide an insight to the therapeutic implications to human health in the future.

scholarly journals The Influence ofTRP53in the Dose Response of Radiation-Induced Apoptosis, DNA Repair and Genomic Stability in Murine Haematopoietic Cells

Dose-Response ◽  
2014 ◽  
Vol 12 (3) ◽  
pp. dose-response.1 ◽  
Author(s):  
Jennifer A. Lemon ◽  
Kristina Taylor ◽  
Kyle Verdecchia ◽  
Nghi Phan ◽  
Douglas R. Boreham
Keyword(s):  
Dna Repair ◽  
Dose Response ◽  
Genomic Stability ◽  
Haematopoietic Cells ◽  
Radiation Induced ◽  
Induced Apoptosis

scholarly journals Evaluation of Calyculin A Effect on γH2AX/53BP1 Focus Formation and Apoptosis in Human Umbilical Cord Blood Lymphocytes

2021 ◽  
Vol 22 (11) ◽  
pp. 5470
Author(s):  
Lucián Zastko ◽  
Anna Račková ◽  
Petra Petrovičová ◽  
Matúš Durdík ◽  
Jakub Míšek ◽  
...  
Keyword(s):  
Dna Repair ◽  
Low Dose ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Low Doses ◽  
Calyculin A ◽  
Focus Formation ◽  
Radiation Induced ◽  
Kinetics Of ◽  
Cord Blood Lymphocytes

Dephosphorylation inhibitor calyculin A (cal A) has been reported to inhibit the disappearance of radiation-induced γH2AX DNA repair foci in human lymphocytes. However, other studies reported no change in the kinetics of γH2AX focus induction and loss in irradiated cells. While apoptosis might interplay with the kinetics of focus formation, it was not followed in irradiated cells along with DNA repair foci. Thus, to validate plausible explanations for significant variability in outputs of these studies, we evaluated the effect of cal A (1 and 10 nM) on γH2AX/53BP1 DNA repair foci and apoptosis in irradiated (1, 5, 10, and 100 cGy) human umbilical cord blood lymphocytes (UCBL) using automated fluorescence microscopy and annexin V-FITC/propidium iodide assay/γH2AX pan-staining, respectively. No effect of cal A on γH2AX and colocalized γH2AX/53BP1 foci induced by low doses (≤10 cGy) of γ-rays was observed. Moreover, 10 nM cal A treatment decreased the number of all types of DNA repair foci induced by 100 cGy irradiation. 10 nM cal A treatment induced apoptosis already at 2 h of treatment, independently from the delivered dose. Apoptosis was also detected in UCBL treated with lower cal A concentration, 1 nM, at longer cell incubation, 20 and 44 h. Our data suggest that apoptosis triggered by cal A in UCBL may underlie the failure of cal A to maintain radiation-induced γH2AX foci. All DSB molecular markers used in this study responded linearly to low-dose irradiation. Therefore, their combination may represent a strong biodosimetry tool for estimation of radiation response to low doses. Assessment of colocalized γH2AX/53BP1 improved the threshold of low dose detection.

scholarly journals Coexistence of SOS-Dependent and SOS-Independent Regulation of DNA Repair Genes in Radiation-Resistant Deinococcus Bacteria

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 924
Author(s):  
Laurence Blanchard ◽  
Arjan de Groot
Keyword(s):  
Dna Repair ◽  
Deinococcus Radiodurans ◽  
Dna Repair Genes ◽  
Lesion Bypass ◽  
Radiation Resistant ◽  
Radiation Induced ◽  
Induced Mutagenesis ◽  
High Doses ◽  
Translesion Polymerases ◽  
Repair Genes

Deinococcus bacteria are extremely resistant to radiation and able to repair a shattered genome in an essentially error-free manner after exposure to high doses of radiation or prolonged desiccation. An efficient, SOS-independent response mechanism to induce various DNA repair genes such as recA is essential for radiation resistance. This pathway, called radiation/desiccation response, is controlled by metallopeptidase IrrE and repressor DdrO that are highly conserved in Deinococcus. Among various Deinococcus species, Deinococcus radiodurans has been studied most extensively. Its genome encodes classical DNA repair proteins for error-free repair but no error-prone translesion DNA polymerases, which may suggest that absence of mutagenic lesion bypass is crucial for error-free repair of massive DNA damage. However, many other radiation-resistant Deinococcus species do possess translesion polymerases, and radiation-induced mutagenesis has been demonstrated. At least dozens of Deinococcus species contain a mutagenesis cassette, and some even two cassettes, encoding error-prone translesion polymerase DnaE2 and two other proteins, ImuY and ImuB-C, that are probable accessory factors required for DnaE2 activity. Expression of this mutagenesis cassette is under control of the SOS regulators RecA and LexA. In this paper, we review both the RecA/LexA-controlled mutagenesis and the IrrE/DdrO-controlled radiation/desiccation response in Deinococcus.

scholarly journals Effects of exposure to low-dose ionizing radiation on changing platelets: a prospective cohort study

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Ning Liu ◽  
Yang Peng ◽  
Xinguang Zhong ◽  
Zheng Ma ◽  
Suiping He ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Ionizing Radiation ◽  
Dose Response ◽  
Low Dose ◽  
Linear Trend ◽  
Hematological Parameters ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Spline Models ◽  
Cumulative Radiation Dose

Abstract Background Numerous studies have concentrated on high-dose radiation exposed accidentally or through therapy, and few involve low-dose occupational exposure, to investigate the correlation between low-dose ionizing radiation and changing hematological parameters among medical workers. Methods Using a prospective cohort study design, we collected health examination reports and personal dose monitoring data from medical workers and used Poisson regression and restricted cubic spline models to assess the correlation between changing hematological parameters and cumulative radiation dose and determine the dose-response relationship. Results We observed that changing platelet of 1265 medical workers followed up was statistically different among the cumulative dose groups (P = 0.010). Although the linear trend tested was not statistically significant (Ptrend = 0.258), the non-linear trend tested was statistically significant (Pnon-linear = 0.007). Overall, there was a correlation between changing platelets and cumulative radiation dose (a change of βa 0.008 × 109/L during biennially after adjusting for gender, age at baseline, service at baseline, occupation, medical level, and smoking habits; 95% confidence interval [CI] = 0.003,0.014 × 109/L). Moreover, we also found positive first and then negative dose-response relationships between cumulative radiation dose and changing platelets by restricted cubic spline models, while there were negative patterns of the baseline service not less than 10 years (− 0.015 × 109/L, 95% CI = − 0.024, − 0.007 × 109/L) and radiation nurses(− 0.033 × 109/L, 95% CI = − 0.049, − 0.016 × 109/L). Conclusion We concluded that although the exposure dose was below the limit, medical workers exposed to low-dose ionizing radiation for a short period of time might have increased first and then decreased platelets, and there was a dose-response relationship between the cumulative radiation dose and platelets changing.

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