low-LET Radiation Research Articles

Excess Relative Risk of Mortality from Diseases of the Circulation System after Irradiation. Report 1. Overview of Reviews and Meta-analysis Declared Effects of Low Doses

A review of two reports is devoted to the problem of the significance of excess relative risks (ERR) per 1 Gy/Sv for mortality from diseases of the circulatory system for various exposed groups from the standpoint of epidemiology and in terms of the effects of low doses of radiation. Report 1 provides an overview of reviews and meta-analyses, together with key studies, on this topic. In most sources, 2005–2021 (publications by M.P. Little with co-workers, and others) reveals an ideological bias towards the effects of low doses of radiation (noted in the titles or summaries of almost all papers), and often there was a lack of understanding about the upper limit of this range accepted by international organizations for low LET radiation (up to 0.1 Gy according to UNSCEAR, ICRP, BEIR, etc.). In selected M.P. Little and co-authors sources for reviews and meta-analyses observed both absurd ERR values per 1 Gy and incorrect recalculations of the risk estimated in the originals at 0.1 Gy. Examples of the incorrectness of such estimations are presented, since ERR per 1 Gy calculated for ranges of lower doses may differ from those for high dose ranges by many times, and this is a systemic phenomenon, despite all the declarations of a linear non-threshold concept. Selection of sources for meta-analyses used by M.P. Little and other authors (2010–2020) violates the principles of homogeneity (groups with radiotherapy (including children with tinea capitis) are combined with miners, liquidators of the Chernobyl accident, etc.), representing an illustration of a meme of critics of meta-analytical approaches (“combination of apples and oranges”). The values of ERR per 1 Gy obtained as a result of meta-analyses for diseases of the circulatory system in general and for their individual types according to epidemiological risk scales (R.R. Monson scale, 1980; 1990) are either insignificant (ERR = 0–0.2), or, rarely, located on the border of weak associations (ERR = 0.2–0.5). An analysis of data from reviews and meta-analyses on the topic did not reveal sources that investigated effects limited to low dose ranges. In almost all cases, with some exceptions (miners with radon exposure, cohorts with absurd risks, etc.), the upper limit of the range for groups in the samples was either medium (0.1–1 Gy) or high (1 Gy). ) doses. An analysis of almost all publications on the topic of Mayak employees (T.V. Azizova with co-workers; 2010–2018; 31 sources) showed a lack of risk studies for groups with low doses of external exposure (up to 0.1 Gy), with the exception of works from 2014 and 2018, in which either reverse or weak effects were established in the absence of dose dependence. Thus, no samples in reviews and meta-analyses, as well as data for Mayak PA, provide material on the correspon-ding effect of low doses, despite the prevailing general idea of its “proof”. It was concluded that one should adhere to the statement of international organizations (USCEAR, ICRP, NCRP, BEIR, etc.) that the threshold for increasing mortality from diseases of the circulatory system is not less than 0.5 Gy, and then raise the issue of their radiation attribution for low doses impractical.

More efficient induction of genotoxicity by high-LET Fe-particle radiation than low-LET X-ray radiation at low doses

ObjectiveTo understand differential effects on induction of genotoxicity and genomic instability (GI) by high-LET particle radiation and low-LET photon radiation, based on ground-based experiments using total body irradiation (TBI) of mice with Fe-particle radiation and X-ray radiation. MethodsTBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation. Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint. Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis. Physiological conditions were also investigated. ResultsTBI, regardless of the type of radiation, caused statistically significant increase in genotoxicity at 1 month after exposure, but did not induce GI at 2 months after exposure even at higher doses (>1.0 Gy). The dose-response curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y ​= ​0.7798 ​+ ​1.7889x– 0.5978x2 (R2 = 0.8109) and y ​= ​0.7421 ​+ ​1.3792x – 0.2588 x2 (R2 = 0.8081), respectively. The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y ​= ​0.7191 ​+ ​1.4545x – 0.4978x2 (R2 = 0.7047) and y ​= ​0.658 ​+ ​1.344x – 0.2531x2 (R2 = 0.7853), respectively. In general, high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses (<0.5 Gy). ConclusionsThese results further confirm that exposure to TBI, even at higher doses and regardless the type of radiation, does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes. These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences from exposure to high-LET radiation at low doses.

Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation.

Exposure to ionizing radiation can occur during medical treatments, from naturally occurring sources in the environment, or as the result of a nuclear accident or thermonuclear war. The severity of cellular damage from ionizing radiation exposure is dependent upon a number of factors including the absorbed radiation dose of the exposure (energy absorbed per unit mass of the exposure), dose rate, area and volume of tissue exposed, type of radiation (e.g., X-rays, high-energy gamma rays, protons, or neutrons) and linear energy transfer. While the dose, the dose rate, and dose distribution in tissue are aspects of a radiation exposure that can be varied experimentally or in medical treatments, the LET and eV are inherent characteristics of the type of radiation. High-LET radiation deposits a higher concentration of energy in a shorter distance when traversing tissue compared with low-LET radiation. The different biological effects of high and low LET with similar energies have been documented in vivo in animal models and in cultured cells. High-LET results in intense macromolecular damage and more cell death. Findings indicate that while both low- and high-LET radiation activate non-homologous end-joining DNA repair activity, efficient repair of high-LET radiation requires the homologous recombination repair pathway. Low- and high-LET radiation activate p53 transcription factor activity in most cells, but high LET activates NF-kB transcription factor at lower radiation doses than low-LET radiation. Here we review the development, uses, and current understanding of the cellular effects of low- and high-LET radiation exposure.

Factors released by low and high-LET irradiated fibroblasts modulate migration and invasiveness of pancreatic cancer cells.

IntroductionRadiotherapy represents a major treatment option for patients with pancreatic cancer, however, its benefits remain limited also due to the ability of cancer cells to migrate to the surrounding tissues. Low-LET ionizing radiation is well known to promote tumor cell migration and invasion, nevertheless, little data provided by studies using high-LET radiation has led to ambiguous findings. What is hypothesized to be fundamental in the modulation of migration of tumor cells exposed to ionizing radiation is the influence of the microenvironment. Therefore, the properties of cells that populate the tumor stroma cannot be ignored when studying the influence of radiation on the migratory and invasive capacity of cancer cells. This is especially important in the case of pancreatic malignancies that are characterized by an abundance of stromal cells, including cancer-associated fibroblasts, which are known to orchestrate the cross-talk with tumor cells.AimThe current study aims to investigate whether the presence of factors released by irradiated fibroblasts affects the migratory and invasive capacity of pancreatic cancer cells exposed to different doses of photons or C-ions.Materials and methodsAsPC-1 and AG01522 cells were irradiated with the same dose of photons or C-ions at room temperature. Through Boyden chamber assay, we tested whether factors secreted by irradiated fibroblasts may influence tumor cell migration, while the invasiveness of AsPC-1 cells was assessed using matrigel precoated inserts in which medium collected from non-irradiated (0 Gy), photon and C-ion irradiated fibroblasts, was added. Data were analyzed by Student t-test using GraphPad software. The mean ± s.d. was determined with a significance level of p<0.05.ResultsIn the presence of conditioned medium collected from 1 Gy and 2 Gy photon irradiated fibroblasts, the number of migrated tumor cells increased (P<0.0360, P<0.0001) but decreased at 4 Gy dose (P<0.002). There was a trend of reduction in migration (P<0.0460, P<0.038, P<0.0024, P<0.0002), as well as a decrease in invasiveness (P<0.0525, P<0.0035, P<0.0868, P<0.0310) after exposure to 0.5 Gy, 1 Gy, 2 Gy and 4 Gy of C-ions.ConclusionsThe presence of irradiated fibroblasts affected the invasiveness capability of pancreatic cancer cells, probably by the reciprocal release of soluble factors whose production is differently modulated after high or low-LET radiation. Understanding the effects of irradiation on the metastatic potential of pancreatic cancer cells is of utmost importance for improving the outcome and tailoring the therapeutic approach. This challenging scenario requires a continuous and multidisciplinary approach that involves clinicians together with researcher experts in oncological and radiation treatment. In the last years, including preclinical experiences in a multidisciplinary approach has proved to be a winning strategy in clinical oncological research.

The effect of linear energy transfer on the early, transient radiolytic oxygen depletion in the radiolysis of water by high-dose-rate irradiating protons

Monte Carlo multi-track chemistry simulations were carried out to study, from a radiation chemistry perspective, the effect of “linear energy transfer” (LET) on the transient yields and concentrations of radiolytic oxygen consumption in the high-dose-rate (∼107 Gy/s) radiolysis of both pure air-saturated (0.25 mmol/L O2) and oxygenated (30 µmol/L O2) cell water, in the interval ∼1 ps–10 µs. Our simulation model consisted of randomly irradiating water with single pulses of 5 MeV (LET ∼ 8 keV/µm), 1.5 MeV (LET ∼ 19.5 keV/µm), and 0.7 MeV (LET ∼ 33 keV/µm) protons at 25 °C. Similar to what is observed with low-LET irradiation (∼300 MeV protons, LET ∼ 0.3 keV/µm), our calculations showed that, in pure, aerated water, the concentration of depleted oxygen, [−O2], exhibits a pronounced maximum around ∼0.1–0.2 µs for all three high-LET irradiating protons studied. This maximum increased markedly with increasing LET. As expected, the effect of adding competing scavengers of both hydrated electrons and•OH radicals on the radiolytic O2depletion in oxygenated cell water (a more bio-mimetic model of cells) irradiated by 5 MeV protons delivered at the same dose rate led to a marked decrease in the maximum of [−O2] around 1 µs. However, contrary to what is observed for low-LET irradiation, we found that the transient O2consumption is quite substantial under high-LET irradiation conditions. This is explained by the fact that, even though their underlying mechanism of action differs, high-LET particles affect radiolysis yields in a similar way to high dose rates.

Low dose hyper-radiosensitivity in normal human cells

Cells usually have different sensitivity to ionising radiation depending on their phase during the cell cycle, particularly at low-LET radiation. The most sensitive phases in the cell cycle are the M- and G2 phases, where S and G1 are the resistant phases. Low doses of radiation can induce various delayed and non-targeted effects, including bystanders (BE) and hyper-radiosensitivity (HRS), in vitro and in vivo. The region of HRS is thought to be formed by an excessive induction of DNA DSBs, which consequently led to a hyper-activation of the DNA repair mechanisms. Such phenomena result in a modification to the Linear Quadratic (LQ) model to include the out-of-fit dose points. At low doses below 1 Gy of radiation, most mammalian cells have shown HRS, which is frequently followed by an Induced-radioresistance (IRR) phenomenon. To confirm the observations of the HRS and IRR effects and identify their start- and endpoints at low doses of X-ray irradiations, the AG1522 normal human fibroblasts cells were irradiated with a range of selected high- and low doses of 0.2, 0.4, 0.6, 1, 2, 3, 4 and 5 Gy with a specific interest at the doses below 1 Gy. The HRS is pronounced at the dose of 0.2 Gy of X-ray irradiation, followed by the IRR phenomenon as the dose increases up to 0.6 Gy. In the context of radiation protection, these results need to be considered during radiotherapy treatment. The presence of the HRS in the survival curves of normal AG1522 cells after X-irradiation maximises the possible advantage of using such low doses to improve clinical outcomes. These data provide further insight into the radiobiological parameters, highlighting the need to refine existing radiobiological parameters to incorporate such effects and modulate dose distributions.

TOPAS-nBio simulation of temperature-dependent indirect DNA strand break yields

Current Monte Carlo simulations of DNA damage have been reported only at ambient temperature. The aim of this work is to use TOPAS-nBio to simulate the yields of DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) produced in plasmids under low-LET irradiation incorporating the effect of the temperature changes in the environment. A new feature was implemented in TOPAS-nBio to incorporate reaction rates used in the simulation of the chemical stage of water radiolysis as a function of temperature. The implemented feature was verified by simulating temperature-dependent G-values of chemical species in liquid water from 20 °C to 90 °C. For radiobiology applications, temperature dependent SSB and DSB yields were calculated from 0 °C to 42 °C, the range of available published measured data. For that, supercoiled DNA plasmids dissolved in aerated solutions containing EDTA irradiated by Cobalt-60 gamma-rays were simulated. TOPAS-nBio well reproduced published temperature-dependent G-values in liquid water and the yields of SSB and DSB for the temperature range considered. For strand break simulations, the model shows that the yield of SSB and DSB increased linearly with the temperature at a rate of (2.94 ± 0.17) × 10−10 Gy–1 Da–1 °C–1 (R 2 = 0.99) and (0.13 ± 0.01) × 10−10 Gy–1 Da–1 °C–1 (R 2 = 0.99), respectively. The extended capability of TOPAS-nBio is a complementary tool to simulate realistic conditions for a large range of environmental temperatures, allowing refined investigations of the biological effects of radiation.

On the effect of dose delivery temporal domain on the biological effectiveness of central nervous system CyberKnife radiosurgery applications: theoretical assessment using the concept of biologically effective dose

Objective: The diversity in technical configuration between clinically available radiosurgery systems, results in accordingly diverse treatment times for the same physical dose prescription, spanning from several min to more than 1 h. This, combined with evidence supporting the impact of dose delivery temporal pattern on the bio-effectiveness of low-LET radiation treatments, challenges the ‘acute exposure’ assumption adopted clinically to estimate the biological outcome of a given treatment scheme under the concept of biologically effective dose (BED). Approach: In this work, the treatment plans of 30 patients underwent CyberKnife radiosurgery for vestibular schwannoma (VS), prescribing a marginal dose of 13 Gy to the tumor, were retrospectively reviewed and the corresponding dose distributions were resolved in the temporal domain. For this purpose, the dose delivery timeline for each treatment was calculated based on relevant treatment plan data and technical specifications of the CyberKnife system, while dosimetry data were independently acquired on a CT-based digital model of each patient using an in-house developed dose calculation algorithm. Main results: Results showed that CyberKnife delivers highly inhomogeneous dose rate distributions in the temporo-spatial domain. This influences the delivered BED levels due to alterations in the sublethal damage repair (SLR) occurring within the treatment session. Using a BED framework involving SLR effects, it was shown that each physical dose iso-surface is associated with a BEDslr range. For the patient cohort studied, a typical range of 2%, with respect to the mean BEDslr value was found at 1σ. Significance: The marginal BEDslr delivered to the tumor by the prescription dose iso-surface deteriorates with treatment time, involving both beam-on time and beam-off gaps. For treatment time, T, between 21 and 50 min, this can be expressed by Compared to the acute exposure approach, a BED ‘loss’ of 21% is associated with the delivery of 13 Gy to the VS-tumor in 35 min.

Study on the radiation detriment

Cancer incidence risks, lifetime effects and radiation detriments are determined for the whole population and various subpopulations as a result of acute and chronic exposure to low-LET radiation, taking into account the risk models, procedures and representative populations provided by ICRP. The results are given for solid cancers in different organs, as well as for soft tissue cancer in bone marrow. For most cancer sites a good agreement is obtained between the results of this study and the values published by the ICRP. The agreement with ICRP values is better for the whole population than for the working age population, where the results are systematically elevated. For chronic exposure, the years of life lost per radiation-induced cancer incidence are generally higher. In particular, this results in a radiation detriment for the whole population that is 30% higher than for acute exposure. The study reveals that risk quantities show a pronounced age dependence. The highest radiation risks are attributed to young persons; the lowest to persons in advanced ages. The total detriment imposed on people in different ages varies by a factor of about 30. The average values provided by the ICRP mask these variations and considerably underestimate radiation risks in childhood and adolescence. This also concerns the determination of the effective dose for persons in these age groups. Unlike the ICRP, which provides different nominal detriments for the whole population and the working age population, the results of this study do not support the use of different detriments for these populations.

Inactivation of SARS-CoV-2 by charged particles for Future Vaccine Production Applications: A Monte Carlo study

The world is still suffering from the SARS-CoV-2 pandemic, and the number of infected people is still growing in many countries in 2022. Although great strides have been made to produce effective vaccines, efforts in this field should be accelerated, particularly due to the emergence of new variants. Using inactivated viruses is a conventional method of vaccine production. High levels of ionizing radiation can effectively inactivate viruses. Recently, studies on SARS-CoV-2 irradiation using low-LET radiations (e.g., gamma rays) have been performed. However, there are insufficient studies on the impact of charged particles on the inactivation of this virus. In this study, a realistic structure of SARS-CoV-2 is simulated by using Geant4 Monte Carlo toolkit, and the effect of electrons, protons, alphas, C-12, and Fe-56 ions on the inactivation of SARS-CoV-2 is investigated. The simulation results indicated that densely ionizing (high-LET) particles have the advantage of minimum number of damaged spike proteins per single RNA break. The RNA breaks induced by hydroxyl radicals produced in the surrounding water medium were significant only for electron beam radiation. Hence, indirect RNA breaks induced by densely ionizing particles is negligible. From a simulation standpoint, alpha particles (with energies up to 30 MeV) as well as C-12 ions (with energies up to 80 MeV/n), and Fe-56 ions (with any energy) can be introduced as particles of choice for effective SARS-CoV-2 inactivation.

Flying without a Net: Space Radiation Cancer Risk Predictions without a Gamma-ray Basis.

The biological effects of high linear energy transfer (LET) radiation show both a qualitative and quantitative difference when compared to low-LET radiation. However, models used to estimate risks ignore qualitative differences and involve extensive use of gamma-ray data, including low-LET radiation epidemiology, quality factors (QF), and dose and dose-rate effectiveness factors (DDREF). We consider a risk prediction that avoids gamma-ray data by formulating a track structure model of excess relative risk (ERR) with parameters estimated from animal studies using high-LET radiation. The ERR model is applied with U.S. population cancer data to predict lifetime risks to astronauts. Results for male liver and female breast cancer risk show that the ERR model agrees fairly well with estimates of a QF model on non-targeted effects (NTE) and is about 2-fold higher than the QF model that ignores NTE. For male or female lung cancer risk, the ERR model predicts about a 3-fold and more than 7-fold lower risk compared to the QF models with or without NTE, respectively. We suggest a relative risk approach coupled with improved models of tissue-specific cancers should be pursued to reduce uncertainties in space radiation risk projections. This approach would avoid low-LET uncertainties, while including qualitive effects specific to high-LET radiation.

Ramsar, Iran, as a Natural Radiobiological Surrogate for Mars.

Terrestrial experiments involving acute exposures of low-LET radiation on inbred lab animals are quick, simple, and inexpensive but are relatively uninformative about the real radiobiological hazards of planned manned space missions. A more predictive model could involve human beings chronically exposed to "space-like" high-LET radiation. Such radiation exposure has been ongoing for thousands of years in Ramsar, Iran, and some other high-LET high background radiation regions on Earth. Examining the health of Ramsar residents can be illuminating and potentially relevant to space missions.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Demonstration of an optically stimulated luminescence (OSL) material with reduced quenching for proton therapy dosimetry: MgB4O7:Ce,Li

The objective of this work is to demonstrate that MgB4O7:Ce,Li, a new optically stimulated luminescence (OSL) dosimetric material, shows improved response for proton therapy dosimetry, with less reduction in luminescence detector efficiency with the particle linear energy transfer (LET). MgB4O7:Ce,Li was synthesized and its luminescence efficiency as a function of LET was characterized for dose-averaged LET values from 0.73 keV/μm up to 74.9 keV/μm using proton, 4He, and 12C ion beams. Commercial Al2O3:C OSLDs were also used for comparison. Monte Carlo simulations were used to predict the material's response in pristine and spread-out Bragg peaks (SOBP), suggesting the MgB4O7:Ce,Li would offer minimum quenching in proton beams of energies relevant to radiotherapy. This prediction was confirmed by irradiations of MgB4O7:Ce,Li and Al2O3:C along SOBPs from proton beams. The results demonstrate that new OSL materials optimized for proton dosimetry can be developed using their dose response to low-LET radiation as a guide during material development.

Incorporation of Low Concentrations of Gold Nanoparticles: Complex Effects on Radiation Response and Fate of Cancer Cells.

(1) Background: In oncology research, a long-standing discussion exists about pros and cons of metal nanoparticle-enhanced radiotherapy and real mechanisms behind the tumor cell response to irradiation (IR) in presence of gold nanoparticles (GNPs). A better understanding of this response is, however, necessary to develop more efficient and safety nanoparticle (NP) types designed to disturb specific processes in tumor cells. (2) Aims and Methods: We combined 3D confocal microscopy and super-resolution single molecule localization microscopy (SMLM) to analyze, at the multiscale, the early and late effects of 10 nm-GNPs on DNA double strand break (DSB) induction and repair in tumor cells exposed to different doses of photonic low-LET (linear energy transfer) radiation. The results were correlated to different aspects of short and long-term cell viability. SkBr3 breast cancer cells (selected for the highest incidence of this cancer type among all cancers in women, and because most breast tumors are treated with IR) were incubated with low concentrations of GNPs and irradiated with 60Co γ-rays or 6 MV X-rays. In numerous post-irradiation (PI) times, ranging from 0.5 to 24 h PI, the cells were spatially (3D) fixed and labeled with specific antibodies against γH2AX, 53BP1 and H3K9me3. The extent of DSB induction, multi-parametric micro- and nano-morphology of γH2AX and 53BP1 repair foci, DSB repair kinetics, persistence of unrepaired DSBs, nanoscale clustering of γH2AX and nanoscale (hetero)chromatin re-organization were measured by means of the mentioned microscopy techniques in dependence of radiation dose and GNP concentration. (3) Results: The number of γH2AX/53BP1 signals increased after IR and an additional increase was observed in GNP-treated (GNP(+)) cells compared to untreated controls. However, this phenomenon reflected slight expansion of the G2-phase cell subpopulation in irradiated GNP(+) specimens instead of enhanced DNA damage induction by GNPs. This statement is further supported by some micro- and nano-morphological parameters of γH2AX/53BP1 foci, which slightly differed for cells irradiated in absence or presence of GNPs. At the nanoscale, Ripley’s distance frequency analysis of SMLM signal coordinate matrices also revealed relaxation of heterochromatin (H3K9me3) clusters upon IR. These changes were more prominent in presence of GNPs. The slight expansion of radiosensitive G2 cells correlated with mostly insignificant but systematic decrease in post-irradiation survival of GNP(+) cells. Interestingly, low GNP concentrations accelerated DSB repair kinetics; however, the numbers of persistent γH2AX/53BP1 repair foci were slightly increased in GNP(+) cells. (4) Conclusions: Low concentrations of 10-nm GNPs enhanced the G2/M cell cycle arrest and the proportion of radiosensitive G2 cells, but not the extent of DNA damage induction. GNPs also accelerated DSB repair kinetics and slightly increased presence of unrepaired γH2AX/53BP1 foci at 24 h PI. GNP-mediated cell effects correlated with slight radiosensitization of GNP(+) specimens, significant only for the highest radiation dose tested (4 Gy).

A simulation approach to predict the calibration curve of low LET radiations for biological dosimetry using the Geant4-DNA toolkit

Ionizing radiation is extensively utilized in various applications; however, it can lead to significant harm to living systems. In this regard, the radiation absorbed dose is usually evaluated by performing biological dosimetry and physical reconstruction of exposure scenarios. But, this is costly, time-consuming, and maybe impractical for a biodosimetry lab to perform biological dosimetry. This study aimed to assess the applicability and reliability of the Geant4-DNA toolkit as a simulation approach to construct a reliable dose-response curve for biodosimetry purposes as an appropriate substitution for experimental measurements. In this matter, the total number of double-strand breaks (DSBs), due to different doses of low LET radiation qualities on DNA molecules, was calculated and converted to the values of dicentric chromosomes using a mechanistic model of cellular response. Then, the number of dicentric chromosomes induced by 200 kVp X-rays were modified by using a semi-empirical scaling factor for compensating the restriction of simulation code to consider what can happen in a real cell. Next, the trend of dicentrics for 137Cs and 60Co were calculated and modified by the above scaling factor. Finally, the dose-response curves for these gamma sources compared to several published experiments. The suggested calibration curves for 137Cs and 60Co followed a linear quadratic equation: Ydic = 0.0054 (± 0.0133) - 0.0089 (± 0.0212) × D + 0.0568 (± 0.0051) × D2 and Ydic = 0.0052 (± 0.0128) - 0.00568 (± 0.0203) × D + 0.0525 (± 0.0049) × D2 respectively. They revealed a satisfactory agreement with the experimental data reported by others. The Geant4 program developed in this work could provide an appropriate tool for predicting the dose-response (calibration) curve for biodosimetry purposes.

Induction of adaptive response in utero by ionizing radiation: A radiation quality dependent phenomenon

Investigation on possible induction of adaptive response (AR) by high-liner energy transfer (LET) particle radiation for protection against low-LET photon radiation-induced detrimental effects has not yet been performed <i>in utero</i>. This study verified if an AR could be induced by high-LET particle radiation from accelerated heavy ions against low-LET X-ray radiation-induced detrimental effects on fetal mice. Total body irradiation of pregnant C57BL/6J mice were performed by delivering a priming dose ranging from 10 mGy to 320 mGy of particle radiation on gestation day 11 followed one day later by a challenge dose at 3500 mGy from X-ray radiation. The monoenergetic beams of carbon, silicon and iron with the LET values of about 15, 55, and 200 KeV/μm, respectively, were examined. Significant suppression by the priming radiation of the detrimental effects (fetal death, malformation, or low body weight) was used as the endpoints for judgment of a successful AR induction on gestation day 18. Existence of AR was not observed. On the other hand, the priming dose of high-LET particle radiation, in some cases, even increased the detrimental effects induced by the challenge dose from low-LET X-ray radiation. Although existence of AR induced by high-LET radiation in cultured mammalian cells<i> in vitro </i> and in certain tissues of laboratory mice <i>in vivo</i> was demonstrated, the present study did not suggest that low dose of high-LET particle radiation could induce an AR in fetal mice <i>in utero</i> under the setup of our experimental system.

Cancer risk following low doses of ionising radiation – Current epidemiological evidence and implications for radiological protection

Recent studies suggest that every year worldwide about a million patients might be exposed to doses of the order of 100 mGy of low-LET radiation, due to recurrent application of radioimaging procedures. This paper presents a synthesis of recent epidemiological evidence on radiation-related cancer risks from low-LET radiation doses of this magnitude. Evidence from pooled analyses and meta-analyses also involving epidemiological studies that, individually, do not find statistically significant radiation-related cancer risks is reviewed, and evidence from additional and more recent epidemiological studies of radiation exposures indicating excess cancer risks is also summarized. Cohorts discussed in the present paper include Japanese atomic bomb survivors, nuclear workers, patients exposed for medical purposes, and populations exposed environmentally to natural background radiation or radioactive contamination. Taken together, the overall evidence summarized here is based on studies including several million individuals, many of them followed-up for more than half a century. In summary, substantial evidence was found from epidemiological studies of exposed groups of humans that ionizing radiation causes cancer at acute and protracted doses above 100 mGy, and growing evidence for doses below 100 mGy. The significant radiation-related solid cancer risks observed at doses of several 100 mGy of protracted exposures (observed, for example, among nuclear workers) demonstrate that doses accumulated over many years at low dose rates do cause stochastic health effects. On this basis, it can be concluded that doses of the order of 100 mGy from recurrent application of medical imaging procedures involving ionizing radiation are of concern, from the viewpoint of radiological protection.

DNA repair inhibitors sensitize cells differently to high and low LET radiation

The aim of this study was to investigate effects of high LET α-radiation in combination with inhibitors of DDR (DNA-PK and ATM) and to compare the effect with the radiosensitizing effect of low LET X-ray radiation. The various cell lines were irradiated with α-radiation and with X-ray. Clonogenic survival, the formation of micronuclei and cell cycle distribution were studied after combining of radiation with DDR inhibitors. The inhibitors sensitized different cancer cell lines to radiation. DNA-PKi affected survival rates in combination with α-radiation in selected cell lines. The sensitization enhancement ratios were in the range of 1.6–1.85 in cancer cells. ATMi sensitized H460 cells and significantly increased the micronucleus frequency for both radiation qualities. ATMi in combination with α-radiation reduced survival of HEK293. A significantly elicited cell cycle arrest in G2/M phase after co-treatment of ATMi with α-radiation and X-ray. The most prominent treatment effect was observed in the HEK293 by combining α-radiation and inhibitions. ATMi preferentially sensitized cancer cells and normal HEK293 cells to α-radiation. DNA-PKi and ATMi can sensitize cancer cells to X-ray, but the effectiveness was dependent on cancer cells itself. α-radiation reduced proliferation in primary fibroblast without G2/M arrest.

Cobalt radiation therapy treatments with opposed plain fields and beam flattening filter

Low LET radiations such as cobalt (1.25 MeV) and 6 MV linac megavoltage gamma/x radiations continue to be a basic facility in a busy radiation therapy department. When the beam profiles in water are carefully scrutinized, linac beams have flattened isodose curves compared to slightly rounded curves in Co-60 beams at all depths. It was speculated that to overcome slight non-uniformity in the edges, as well as slight variations inside the planning target volume (PTV), a beam flattening filter may be preferable to be used along with plain radiotherapy fields. A pilot study of clinical use of beam flattener in cobalt beam is reported. A flattening filter (FF) was locally made out of dental wax, for 20 x 20cm field, in the 780E Telecobalt machine (M/s MDS Nordian, Canada). Beam profiles with and without FF were measured using water phantom, to confirm the filter efficiency. Both manual and Radiation Field (RFA) methods in water phantom confirmed efficacy of wax filter. This flattened beam was used in the treatments of Uterine Cervix and Oesophagus cancers, (25 patients each) with a measured filter transmission factor 0.805 in treatment plans. All the patients completed the prescribed dose of 50Gy in 25 fractions for Ca Cervix and 50Gy/25 fractions or 50.4Gy/28 fractions for Ca Oesophagus; at 5 fractions/ week treatment regimens. Case records of these patients retrospectively verified did not reveal any untoward associated morbidity on routine clinical follow ups during treatment or immediate follow up. As multi-leaf collimated cobalt beam also has built in rounded beam profiles, outcome of this work implemented in clinical applications add to new research knowledge. As cervix, head and neck, oesophagus malignancies form significant percentage of radiation oncology treatments, results of this present work will benefit many conventional treatments. It is strongly recommended that the clinical efficacy of FF Cobalt treatments be investigated in a controlled clinical trial, by random allotments with FF plain fields, with output corrections.