Abstract:
:This work provides a description of a new interaction, cross-section-based model for radiation-induced cellular inactivation, sublethal damage, DNA repair and cell survival, with the ability to more accurately elucidate different radiation-response phenomena. The principal goal of this work is to describe the damage-induction cross sections, as well as repair and survival, as Poisson processes with two main types of damage: mild damage that can be rapidly handled by the most basic repair processes; and more complex damage requiring longer repair times and the high-fidelity homologous recombination (HR) repair process to ensure accuracy and safety in the survival. This work is unique in its use of Poisson statistics to quantify the main repairable cell compartments that are exposed to simple and more complex sublethal hits, the cross section of which determines what is homologically and non-homologically repairable. The new method is applied to central radiation damage and survival data, such as in vitro cellular repair and survival with key DNA repair genes knocked out, low-dose hypersensitivity (LDHS), change in survival over the cell cycle, and variation with linear energy transfer (LET) for densely ionizing ions, all results supporting our basic assumptions. Among the results, it was shown that less than 1% of the simple DSBs are lethal at approximately 2 Gy and below for sparsely ionizing radiations, but their δ-electron track ends of between 1.5 and 0.5 keV can deliver 0.5 MGy to a few hundred nm3 volumes, mainly due to multiple scatter detours and multiple secondary electrons. They can cause dual double-strand breaks (DSBs) on the periphery of nucleosomes that are the most common multiply damaged sites, with an average of 1-2 δ-electron track ends per cell nucleus at 2 Gy. LDHS is most likely due to the normal lack of fast, efficient repair of sublethal damage below approximately 0.5 Gy, and requires largely intact key DNA repair genes to achieve significant repair recovery at higher doses. The new repair model describes this phenomenon quite accurately. Cells with key non-homologous end joining (NHEJ) genes knocked-out, lose LDHS but provoke HR repair, and cells with HR genes knocked out may lose some LDHS, but provoke NHEJ repair. The DNA duplication during the S phase results in a direct doubling as well of the total and sublethal hit cross sections. For the lowest LET carbon ions, NHEJ is reduced to where it is almost eliminated at maximum relative biological effectiveness (RBE), while HR is induced more than by X rays, due to complex damage and misrepair of DSBs produced by numerous δ electrons. The use of a lower LET such as electrons or photons during the final week of radiation treatment may potentially maximize complication-free cure. Optimally-designed weekly fractionation schedules are proposed to maximize the DNA repair potential in normal tissues. Additionally, the optimal therapeutic ion species, LET, apoptosis and permanent growth arrest/senescence window is identified with helium, lithium and boron ions and LETs at approximately 15-55 eV/nm, to maximize these quantities in the tumor and minimize them in the normal tissues, resulting in a very high probability of complication-free cure.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Brahme Adoi
10.1667/RADE-20-00052.1subject
Has Abstractpub_date
2020-09-16 00:00:00pages
202-235issue
3eissn
0033-7587issn
1938-5404pii
439623journal_volume
194pub_type
杂志文章abstract::1. A survival curve for the colony-forming ability of mouse bone marrow cells irradiated in vivo with Co60 gamma-rays has been obtained. The curve may be characterized by D0 of 95 rads and an extrapolation number of 1.5. 2. Comparison with the survival curve obtained for irradiated in vitro indicated a statistically s...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1962-06-01 00:00:00
abstract::Little computational or experimental information is available on site-specific hydroxyl attack probabilities to DNA. In this study, an atomistic stochastic model of OH radical reactions with DNA was developed to compute relative OH attack probabilities at individual deoxyribose hydrogen atoms. A model of the self-comp...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2002)157[0038:ssoatt]2.0.co;2
更新日期:2002-01-01 00:00:00
abstract::Transforming growth factor-β-activated kinase 1 (TAK1) appears to play a role in inhibiting apoptotic death in response to multiple stresses. To assess the role of TAK1 in X-ray induced apoptosis and cell death, we irradiated parental and siRNA-TAK1-knockdown HeLa cells. Changes in gene expression levels with and with...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/rr2792.1
更新日期:2012-06-01 00:00:00
abstract::Radiation nephropathy is one of the common late effects in cancer survivors who received radiotherapy as well as in victims of radiation accidents. The clinical manifestations of radiation nephropathy occur months after exposure. To date, there are no known early biomarkers to predict the future development of radiati...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR14828.1
更新日期:2017-12-01 00:00:00
abstract::In pathogen-free mice, but not standard conventionally housed laboratory rodents, two distinctly different modes of early radiation lethality can be identified by modifying the irradiation technique (total-body versus abdominal irradiation) or by therapeutic intervention such as rescue of total-body-irradiated mice wi...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::There is experimental evidence that ultrasoft X rays (0.1-5 keV) show a higher biological effectiveness than high-energy photons. Similar to high-LET radiation, this is attributed to a rather localized dose distribution associated with a considerably smaller range of secondary electrons, which results in an increasing...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR14653.1
更新日期:2018-01-01 00:00:00
abstract::During the pulsed-electron beam direct grafting of neat styrene onto poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) substrate, the radiolytically-produced styryl and carbon-centered FEP radicals undergo various desired and undesired competing reactions. In this study, a high-dose rate is used to impede the und...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR15006.1
更新日期:2018-09-01 00:00:00
abstract::The aim of this study was to test the efficacy of captopril, an angiotensin-converting enzyme inhibitor and a known suppressor of fibrosis, in preventing late radiation-induced cardiac pathology. Myocardial functional, histochemical and ultrastructural-morphometric studies were done on perfused hearts of rats isolated...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Radiation exposure causes DNA breaks leading to structural chromosome aberrations that can be carcinogenic. Lifetime cancer risks are elevated in irradiated children compared to similarly exposed adults. To determine the extent to which age influences the frequency and types of chromosome damage in response to ionizin...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR13598.1
更新日期:2014-06-01 00:00:00
abstract::Dose-response relationships observed in laboratory animals can be used to identify possible human risk factors and may also be used in a quantitative manner when human data are not available. This paper presents an analysis of the dose dependency of osteosarcoma incidence in beagle dogs given a single inhalation expos...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Alteration of adhesion molecule expression on endothelial cells has a direct connection with ionizing radiation-induced atherosclerosis, which is an adverse effect observed after radiotherapy. However, minimal attention has been given to monocytes/macrophages role in atherosclerosis development, which are exposed to t...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR3119.1
更新日期:2013-01-01 00:00:00
abstract::Chinese hamster V79 cells grown for several hours in suspension culture form spheroids which are more resistant to killing by ionizing radiation than cells grown on petri dishes, a phenomenon known as the "contact effect." Previous results using the alkali-unwinding assay as a measure of DNA damage have implicated dif...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::To ensure the high-fidelity transmission by reproductive cells of genetic information from generation to generation, cells have evolved surveillance systems to eliminate genomic lesions by inducing cell suicide and/or DNA repair. In this report, gamma-ray-induced cell death was investigated using the medaka fish, Oryz...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2002)157[0386:acsisf]2.0.co;2
更新日期:2002-04-01 00:00:00
abstract::Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme A. GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellul...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Cellular and molecular repair was studied at 23 degrees C using split-dose recovery and alkaline elution techniques, respectively, as a function of cellular oxygen and nutrient conditions. Hypoxic cells (0.001% O2) in full medium showed a partial reduction in the level of sublethal damage (SLD) repair relative to aera...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::The present study, the ninth in a series that began in 1961, extends the time of surveillance 3 more years and covers the period 1950-1985. It is based on the recently revised doses, termed the DS86. The impact of the change from the T65D to the DS86 on the dose-response relationships for cancer mortality was describe...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Metallothionein (MT), the synthesis of which can be induced by metalloelement administration, is a known radical scavenger. This study investigated the possible protective effect of MT against acute radiation injury. Manganese chloride (10 mg of manganese/kg) was administered intraperitoneally to male C3H/He mice 24 h...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::The purpose of this paper is to validate a metabolic model describing the kinetics of tritium in man. The validation is based on measurements of background levels of loose and bound tritium in Italian subjects and their diets. Model predictions are compared with empirical measurements of tritium in human urine and tis...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
abstract::Water:n-octanol partition coefficients (KD) were determined for a series of radioprotective thiols to ascertain whether these could be used to estimate reliably their rates of uptake into mammalian cells by passive diffusion. Values of KD determined for thiols in 0.1 M potassium phosphate, pH 7.4, at 22 degrees C were...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Exposure of humans and rodents to radiofrequency (RF) cell phone fields has been reported to alter a number of stress- related parameters. To study this potential relationship in more detail, tube-restrained immobilized Fischer 344 rats were exposed in the near field in a dose-dependent manner to pulse-modulated (11 p...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2001)155[0584:eoiace]2.0.co;2
更新日期:2001-04-01 00:00:00
abstract::Abstract Pataky, K., Villanueva, G., Liani, A., Zgheib, O., Jenkins, N., Halazonetis, D. J., Halazonetis, T. D. and Brugger, J. Microcollimator for Micrometer-Wide Stripe Irradiation of Cells Using 20-30 keV X Rays. Radiat. Res. 172, 252-259 (2009). The exposure of subnuclear compartments of cells to ionizing radiatio...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR1483.1
更新日期:2009-08-01 00:00:00
abstract::We have investigated how radiation quality affects the induction of chromosomal aberrations in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated high charge and energy (HZE) particles including oxygen, neon, silicon, titanium and iron. Chromosome damage was assessed using thr...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR3291.1
更新日期:2013-07-01 00:00:00
abstract::Low doses of ionizing radiation to cells and animals may induce adaptive responses that reduce the risk of cancer. However, there are upper dose thresholds above which these protective adaptive responses do not occur. We have now tested the hypothesis that there are similar lower dose thresholds that must be exceeded ...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR1414.1
更新日期:2008-12-01 00:00:00
abstract::The immunocytochemical response to DNA damage induced by low-energy bismuth and carbon ions was investigated in normal human fibroblasts. Inside the nuclei, the traversing charged particles lead to the accumulation of proteins related to DNA lesions and repair along the ion trajectories. Irradiation under a standard g...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2003)159[0676:biohct]2.0.co;2
更新日期:2003-05-01 00:00:00
abstract::The effect of ionizing radiation on the survival of bovine aortic endothelial (BAE) cells was determined by the in vitro colony formation method. The BAE cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% calf serum, antibiotics, and growth factors obtained from the culture of mouse...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::In the event of a radiation accident or attack, it will be imperative to quickly assess the amount of radiation exposure to accurately triage victims for appropriate care. RNA-based radiation dosimetry assays offer the potential to rapidly screen thousands of individuals in an efficient and cost-effective manner. Howe...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/rr1977.1
更新日期:2011-02-01 00:00:00
abstract::Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs an...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/r3016
更新日期:2003-07-01 00:00:00
abstract::To elucidate the nature and kinetics of DNA strand breaks caused by low-energy Auger electron emitters, we compared the yields of DNA breaks in supercoiled pUC19 DNA in the presence of the (.)OH scavenger dimethyl sulfoxide (DMSO) after the decay of (125)I (1) in proximity to DNA after minor-groove binding ((125)I-iod...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has gr...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR15083.1
更新日期:2018-09-01 00:00:00
abstract::Both plant senescence and plant response to ionizing radiation involve changes in gene expression and epigenetic profiles, that rely on the formation of reactive oxygen species. However, how the developmental stage of a plant affects its response to ionizing radiation has not been extensively studied. In this study, o...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR13840.1
更新日期:2015-02-01 00:00:00