Monte carlo simulation study on the dose and dose-averaged linear energy transfer distributions in carbon ion radiotherapy.

Dose-averaged linear energy transfer (LETd) is conventionally evaluated from the relative biological effectiveness (RBE)-LETd fitted function used in the treatment planning system. In this study, we calculated the physical doses and their linear energy transfer (LET) distributions for patterns of typical CIRT beams using Monte Carlo (MC) simulation. The LETd was then deduced from the MC simulation and compared with that obtained from the conventional method. The two types of LETd agreed well with each other, except around the distal end of the spread-out Bragg peak. Furthermore, an MC simulation was conducted with the material composition of water and realistic materials. The profiles of physical dose and LETd were in good agreement for both techniques. These results indicate that the previous studies to analyze the minimum LETd in CIRT cases are valid for practical situations, and the material composition conversion to water little affects the dose distribution in the irradiation field.

Development of DynamicMC for PHITS Monte Carlo package.

Previously, we have developed DynamicMC for modeling relative movement of Oak Ridge National Laboratory phantom in a radiation field for the Monte Carlo N-Particle package (Health Physics. 2023,124(4):301-309). Using this software, three-dimensional dose distributions in a phantom irradiated by a certain mono-energetic (Mono E) source can be deduced through its graphical user interface. In this study, we extended DynamicMC to be used in combination with the Particle and Heavy Ion Transport code System (PHITS) by providing it with a higher flexibility for dynamic movement for an anthropomorphic phantom. For this purpose, we implemented four new functions into the software, which are (1) to generate not only Mono E sources but also those having an energy spectrum of an arbitrary radioisotope (2) to calculate the absorbed doses for several radiologically important organs (3) to automatically average the calculated absorbed doses along the path of the phantom and (4) to generate user-defined slab shielding materials. The first and third items utilize the PHITS-specific modalities named radioisotope-source and sumtally functions, respectively. The computational cost and complexity can be dramatically reduced with these features. We anticipate that the present work and the developed open-source tools will be in the interest of nuclear radiation physics community for research and teaching purposes.

Comparison of dose and risk estimates between ISS Partner Agencies for a 30-day lunar mission.

The International Partner Agencies of the International Space Station (ISS) present a comparison of the ionizing radiation absorbed dose and risk quantities used to characterize example missions in lunar space. This effort builds on previous collaborative work that characterizes radiation environments in space to support radiation protection for human spaceflight on ISS in low-Earth orbit (LEO) and exploration missions beyond (BLEO). A "shielded" ubiquitous galactic cosmic radiation (GCR) environment combined with--and separate from--the transient challenge of a solar particle event (SPE) was modelled for a simulated 30-day mission period. Simple geometries of relatively thin and uniform shields were chosen to represent the space vehicle and other available shielding, and male or female phantoms were used to represent the body's self-shielding. Absorbed dose in organs and tissues and the effective dose were calculated for males and females. Risk parameters for cancer and other outcomes are presented for selected organs. The results of this intracomparison between ISS Partner Agencies itself provide insights to the level of agreement with which space agencies can perform organ dosimetry and calculate effective dose. This work was performed in collaboration with the advisory and guidance efforts of the International Commission on Radiological Protection (ICRP) Task Group 115 and will be presented in an ICRP Report.

A step-by-step simulation code for estimating yields of water radiolysis species based on electron track-structure mode in the PHITS code.

Objective. Time-dependent yields of chemical products resulting from water radiolysis play a great role in evaluating DNA damage response after exposure to ionizing radiation. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo simulation code for radiation transport, which simulates atomic interactions originating from discrete energy levels of ionizations and electronic excitations as well as molecular excitations as physical stages. However, no chemical code for simulating water radiolysis products exists in the PHITS package.Approach.Here, we developed a chemical simulation code dedicated to the PHITS code, hereafter calledPHITS-Chemcode, which enables the calculation of theGvalues of water radiolysis species (•OH, eaq-, H2, H2O2etc) by electron beams.Main results.The estimatedGvalues during 1 µs are in agreement with the experimental ones and other simulations. ThisPHITS-Chemcode also simulates the radiolysis in the presence of OH radical scavengers, such as tris(hydroxymethyl)aminomethane and dimethyl sulfoxide. Thank to this feature, the contributions of direct and indirect effects on DNA damage induction under various scavenging capacities can be analyzed.Significance.This chemical code coupled with PHITS could contribute to elucidating the mechanism of radiation effects by connecting physical, physicochemical, and chemical processes.

Subfoveal perfluorocarbon liquid droplet can be removed without puncturing the retina.

Subfoveal perfluorocarbon liquid (PFL) is a vision-threatening complication that requires removal as safely as possible. We experienced a surgical case of proliferative vitreoretinopathy, in which a subfoveal PFL droplet was removed through the fovea, without puncturing the retina. In this case, although the retina was completely attached after primary vitrectomy and cataract removal, a subfoveal PFL droplet was found. At the second surgery, after peeling the internal limiting membrane, the droplet was passively aspirated by placing a 25-gauge blunt needle on the surface of the retina. This useful technique avoids puncturing the retina and does not require the patient to maintain a specific position postoperatively.

Fetal and Maternal Atomic Bomb Survivor Dosimetry Using the J45 Pregnant Female Phantom Series: Considerations of the Kneeling and Lying Posture with Comparisons to the DS02 System.

ABSTRACT: Organ dosimetry data of the atomic bomb survivors and the resulting cancer risk models derived from these data are currently assessed within the DS02 dosimetry system developed through the Joint US-Japan Dosimetry Working Group. In DS02, the anatomical survivor models are limited to three hermaphroditic stylized phantoms-an adult (55 kg), a child (19.8 kg), and an infant (9.7 kg)-that were originally designed for the preceding DS86 dosimetry system. As such, organ doses needed for assessment of in-utero cancer risks to the fetus have continued to rely upon the use of the uterine wall in the adult non-pregnant stylized phantom as the dose surrogate for all fetal organs regardless of gestational age. To address these limitations, the Radiation Effects Research Foundation (RERF) Working Group on Organ Dose (WGOD) has established the J45 (Japan 1945) series of high-resolution voxel phantoms, which were derived from the UF/NCI series of hybrid phantoms and scaled to match mid-1940s Japanese body morphometries. The series includes male and female phantoms-newborn to adult-and four pregnant female phantoms at gestational ages of 8, 15, 25, and 38 wk post-conception. In previous studies, we have reported organ dose differences between those reported by the DS02 system and those computed by the WGOD using 3D Monte Carlo radiation transport simulations of atomic bomb gamma-ray and neutron fields for the J45 phantoms series in their traditional "standing" posture, with some variations in their facing direction relative to the bomb hypocenter. In this present study, we present the J45 pregnant female phantoms in both a "kneeling" and "lying" posture and assess the dosimetric impact of these more anatomically realistic survivor models in comparison to current organ doses given by the DS02 system. For the kneeling phantoms facing the bomb hypocenter, organ doses from bomb source photon spectra were shown to be overestimated by the DS02 system by up to a factor of 1.45 for certain fetal organs and up to a factor of 1.17 for maternal organs. For lying phantoms with their feet in the direction of the hypocenter, fetal organ doses from bomb source photon spectra were underestimated by the DS02 system by factors as low as 0.77, while maternal organ doses were overestimated by up to a factor of 1.38. Organs doses from neutron contributions to the radiation fields exhibited an increasing overestimation by the DS02 stylized phantoms as gestational age increased. These discrepancies are most evident in fetal organs that are more posterior within the mother's womb, such as the fetal brain. Further analysis revealed that comparison of these postures to the original standing posture indicate significant dose differences for both maternal and fetal organ doses depending on the type of irradiation. Results from this study highlight the degree to which the existing DS02 system can differ from organ dosimetry based upon 3D radiation transport simulations using more anatomically realistic models of those survivors exposed during pregnancy.

Improvement of the hybrid approach between Monte Carlo simulation and analytical function for calculating microdosimetric probability densities in macroscopic matter.

Objective. Estimation of the probability density of the microdosimetric quantities in macroscopic matter is indispensable for applying the concept of microdosimetry to medical physics and radiological protection. The Particle and Heavy Ion Transport code System (PHITS) enables estimating the microdosimetric probability densities due to its unique hybrid modality between the Monte Carlo and analytical approaches called the microdosimetric function. It can convert the deposition energies calculated by the macroscopic Monte Carlo radiation transport simulation to microdosimetric probability densities in water using an analytical function based on the track-structure simulations.Approach. In this study, we improved this function using the latest track-structure simulation codes implemented in PHITS. The improved function is capable of calculating the probability densities of not only the conventional microdosimetric quantities such as lineal energy but also the number of ionization events occurring in a target site, the so-called ionization cluster size distribution, for arbitrary site diameters from 3 nm to 1µm.Main results. The accuracy of the improved function was well verified by comparing the microdosimetric probability densities measured by tissue-equivalent proportional counters with the corresponding data calculated in this study. Test calculations for clonogenic cell survival using the improved function coupled with the modified microdosimetric kinetic model suggested a slight increase of its relative biological effectiveness compared with our previous estimations. As a new application of the improved function, we calculated the relative biological effectiveness of the single-strand break and double-strand break yields for proton irradiations using the updated PHITS coupled with the simplified DNA damage estimation model, and confirmed its equivalence in accuracy and its superiority in computational time compared to our previously proposed method based on the track-structure simulation.Significance. From these features, we concluded that the improved function could expand the application fields of PHITS by bridging the gap between microdosimetry and macrodosimetry.

Fetal atomic bomb survivor dosimetry using the J45 series of pregnant female phantoms with realistic survivor exposure scenarios: comparisons to dose estimates in the DS02 system.

A significant source of information on radiation-induced biological effects following in-utero irradiation stems from studies of atomic bomb survivors who were pregnant at the time of exposure in Hiroshima, and to a lesser extent, from survivors in Nagasaki. Dose estimates to the developing fetus for these survivors have been assigned in prior dosimetry systems of the Radiation Effects Research Foundation as the dose to the uterine wall within the non-pregnant adult stylized phantom, originally designed for the dosimetry system DS86 and then carried forward in DS02. In a prior study, a new J45 (Japanese 1945) series of high-resolution phantoms of the adult pregnant female at 8 weeks, 15 weeks, 25 weeks, and 38-weeks post-conception was presented. Fetal and maternal organ doses were estimated by computationally exposing the pregnant female phantom series to DS02 free-in-air cumulative photon and neutron fluences at three distances from the hypocenter at both Hiroshima and Nagasaki under idealized frontal (AP) and isotropic (ISO) particle incidence. In this present study, this work was extended using realistic angular fluences (480 directions) from the DS02 system for seven radiation source terms, nine different radiation dose components, and five shielding conditions. In addition, to explore the effects of fetal position within the womb, four new phantoms were created and the same irradiation scenarios were performed. General findings are that the current DS02 fetal dose surrogate overestimates values of fetal organ dose seen in the J45 phantoms towards the cranial end of the fetus, especially in the later stages of pregnancy. For example, for in-open exposures at 1000 m in Hiroshima, the ratio of J45 fetal brain dose to DS02 uterine wall dose is 0.90, 0.82, and 0.70 at 15 weeks, 25 weeks, and 38-weeks, respectively, for total gamma exposures, and are 0.64, 0.44, and 0.37 at these same gestational ages for total neutron exposures. For organs in the abdominal and pelvic regions of the fetus, dose gradients across gestational age flatten and later reverse, so that DS02 fetal dosimetry begins to underestimate values of fetal organ dose as seen in the J45 phantoms. For example, for the same exposure scenario, the ratios of J45 fetal kidney dose to DS02 uterine wall dose are about 1.09 from 15 to 38 weeks for total gamma dose, and are 1.30, 1.56, and 1.75 at 15 weeks, 25 weeks, and 38 weeks, respectively, for the total neutron dose. Results using the new fetal positioning phantoms show this trend reversing for a head-up, breach fetal position. This work supports previous findings that the J45 pregnant female phantom series offers significant opportunities for gestational age-dependent assessment of fetal organ dose without the need to invoke the uterine wall as a fetal organ surrogate.

Modelling oxygen effects on the in- and out-of-field radiosensitivity of cells exposed to intensity-modulated radiation fields.

Objective. The delivery of intensity-modulated radiation fields has improved the conformity of dose to tumour targets during radiotherapy (RT). Previously, it has been shown that intercellular communication between cells positioned in- and outside of the radiation field impacts cellular radiosensitivity under hypoxic and normoxic conditions. However, the mechanism of intercellular communication in hypoxia remains to be fully understood. In this study, the cell-killing effects of intercellular communication in hypoxia were modelled in an effort to better understand the underlying mechanisms of response.Approach. By irradiating a 50% area of the culture dish (half-field exposure), experimental dose-response curves for cell survival and residual DNA double-strand breaks (DSBs) were generated in prostate (DU145) and non-small cell lung cancer (H1299) cells. The oxygen enhancement ratio (OER) was determined from early DSB yields (corresponding to relative direct damage) and used to model the in- and out-of-field radiosensitivity.Main results. The developed integrated microdosimetric-kinetic (IMK) model successfully predicted the experimental dose responses for survival and lethal lesions, and provides a mechanistic interpretation that the probability of hits for releasing cell-killing signals is dependent on oxygen. This experimental and modelling study also suggests that residual DSBs correspond to logarithmic survival fraction (meaning lethal lesions) for in- and out-of-field cells. Our data suggest that the OER value determined using uniform-field exposure can be applied to predict the in- and out-of-field radiosensitivity of cells following exposure to intensity modulated beams.Significance. The developed IMK model facilitates a more precise understanding of intercellular signalling following exposure to intensity-modulated radiation fields.

Prospective comparison of accuracy of intraocular lens calculation formulas in phacovitrectomy: a pilot study in a real-world clinical practice.

PURPOSE: To compare the accuracy of intraocular lens (IOL) power calculations among IOL formulas after phacovitrectomy. METHODS: We prospectively enrolled 206 eyes of 206 patients who underwent 25-gauge phacovitrectomy, without gas tamponade, for macular pathology. Pre-operative optical biometry used the IOLMaster 700 to calculate the IOL power with the new formulas, i.e. the Barrett Universal II (BU II), Emmetropia Verifying Optical version 2.0, Hill-Radial Basis Function (RBF) version 3.0, Kane, and Ladas Super Formula, and conventional formulas, i.e. Haigis, Hoffer Q, Holladay 1, Holladay 2, and Sanders-Retzlaff-Kraff/T (SRK/T). A single-piece foldable IOL was implanted in all cases. Manifest refractions were measured before and 3 months after surgery. RESULTS: The BU II formula showed the lowest standard deviation and mean and median absolute errors and had the highest percentage of eyes with a refractive prediction error within ± 0.25 D. The absolute error was significantly lower with the four new formulas, except the Hill-RBF, than with the Hoffer Q (all p = ≤ 0.010) and Holladay 1 formulas (all p = < 0.010). The absolute error with the BU II formula was also lower than that with the Holladay 2 (p = 0.012) and SRK/T (p = 0.024) formulas. CONCLUSION: Overall, the new IOL formulas, except the Hill-RBF, were superior to some of the conventional formulas for calculating IOL power in phacovitrectomy.

Development of a method for calculating effective displacement damage doses in semiconductors and applications to space field.

The displacement damage dose (DDD) is a common index used to predict the life of semiconductor devices employed in space-based environments where they will be exposed to radiation. The DDD is commonly estimated from the non-ionizing energy loss based on the Norgett-Robinson-Torrens (NRT) model, although a new definition for a so-called effective DDD considers the molecular dynamic (MD) simulation with the amorphization in semiconductors. The present work developed a new model for calculating the conventional and effective DDD values for silicon carbide (SiC), indium arsenide (InAs), gallium arsenide (GaAs) and gallium nitride (GaN) semiconductors. This model was obtained by extending the displacement per atom tally implemented in the particle and heavy ion transport code system (PHITS). This new approach suggests that the effective DDD is higher than the conventional DDD for arsenic-based compounds due to the amorphization resulting from direct impacts, while this relationship is reversed for SiC because of recombination defects. In the case of SiC and GaN exposed to protons, the effective DDD/conventional DDD ratio decreases with proton energy. In contrast, for InAs and GaAs, this ratio increases to greater than 1 at proton energies up to 100 MeV and plateaus because the defect production efficiency, which is the ratio of the number of stable displacements at the end of collision cascade simulated by MD simulations to the number of defects calculated by NRT model, does not increase at damage energy values above 20 keV. The practical application of this model was demonstrated by calculating the effective DDD values for semiconductors sandwiched between a thin glass cover and an aluminum plate in a low-Earth orbit. The results indicated that the effective DDD could be dramatically reduced by increasing the glass cover thickness to 200 µm, thus confirming the importance of shielding semiconductor devices used in space. This improved PHITS technique is expected to assist in the design of semiconductors by allowing the effective DDD values for various semiconductors having complex geometries to be predicted in cosmic ray environments.

Application of a simple DNA damage model developed for electrons to proton irradiation.

Proton beam therapy allows irradiating tumor volumes with reduced side effects on normal tissues with respect to conventional x-ray radiotherapy. Biological effects such as cell killing after proton beam irradiations depend on the proton kinetic energy, which is intrinsically related to early DNA damage induction. As such, DNA damage estimation based on Monte Carlo simulations is a research topic of worldwide interest. Such simulation is a mean of investigating the mechanisms of DNA strand break formations. However, past modellings considering chemical processes and DNA structures require long calculation times. Particle and heavy ion transport system (PHITS) is one of the general-purpose Monte Carlo codes that can simulate track structure of protons, meanwhile cannot handle radical dynamics simulation in liquid water. It also includes a simple model enabling the efficient estimation of DNA damage yields only from the spatial distribution of ionizations and excitations without DNA geometry, which was originally developed for electron track-structure simulations. In this study, we investigated the potential application of the model to protons without any modification. The yields of single-strand breaks, double-strand breaks (DSBs) and the complex DSBs were assessed as functions of the proton kinetic energy. The PHITS-based estimation showed that the DSB yields increased as the linear energy transfer (LET) increased, and reproduced the experimental and simulated yields of various DNA damage types induced by protons with LET up to about 30 keVµm-1. These results suggest that the current DNA damage model implemented in PHITS is sufficient for estimating DNA lesion yields induced after protons irradiation except at very low energies (below 1 MeV). This model contributes to evaluating early biological impacts in radiation therapy.

Comparison of the Therapeutic Effects of [211At]NaAt and [131I]NaI in an NIS-Expressing Thyroid Cancer Mouse Model.

Astatine (211At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (131I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [211At]NaAt and [131I]NaI. In vitro analysis of a double-stranded DNA break (DSB) and colony formation assay were performed using K1-NIS cells. The therapeutic effect was compared using K1-NIS xenograft mice administered with [211At]NaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and [131I]NaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The [211At]NaAt induced higher numbers of DSBs and had a more reduced colony formation than [131I]NaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both [211At]NaAt and [131I]NaI. In [211At]NaAt, a stronger tumour-growth suppression was observed, while tumour regrowth was not observed until 18, 25, and 46 days after injection of 0.4, 0.8, and 1.2 MBq of [211At]NaAt, respectively. While in [131I]NaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of [211At]NaAt suggests the promising clinical applicability of targeted alpha therapy using [211At]NaAt in patients with differentiated thyroid cancer refractory to standard [131I]NaI treatment.

Development of the DICOM-based Monte Carlo dose reconstruction system for a retrospective study on the secondary cancer risk in carbon ion radiotherapy.

Objective.A retrospective study on secondary cancer risk on carbon ion radiotherapy (CIRT) is ongoing at the Heavy Ion Medical Accelerator in Chiba (HIMAC). The reconstruction of the whole-body patient dose distribution is the key issue in the study because dose distribution only around the planning target volume was evaluated in the treatment planning system.Approach.We therefore developed a new dose reconstruction system based on the Particle and Heavy Ion Transport code System (PHITS) coupled with the treatment plan DICOM data set by extending the functionalities of RadioTherapy package based on PHITS (RT-PHITS). In the system, the geometry of patient-specific beam devices such as the range shifter, range compensator, and collimators as well as the individual patient's body are automatically reconstructed. Various functions useful for retrospective analysis on the CIRT are implemented in the system, such as those for separately deducing dose contributions from different secondary particles and their origins.Main results.The accuracy of the developed system was validated by comparing the dose distribution to the experimental data measured in a water tank and using a treatment plan on an anthropomorphic phantom.Significance.The extended RT-PHITS will be used in epidemiological studies based on clinical data from HIMAC.

Longitudinal Change in Retinal Nerve Fiber Layer Thickness and Its Association With Central Retinal Sensitivity After Epiretinal Membrane Surgery.

PURPOSE: To investigate the longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) thickness after epiretinal membrane (ERM) vitrectomy with internal limiting membrane (ILM) peeling, examine associations between pRNFL thickness and central retinal sensitivity, and identify predictors of postoperative pRNFL thickness. DESIGN: Prospective, observational, cohort study. METHODS: This study enrolled 82 eyes of 82 Japanese patients that underwent surgery for unilateral idiopathic ERM, with their fellow eyes as controls. pRNFL thickness was measured in 4 (superior, temporal, inferior, and nasal) quadrants preoperatively and at 1, 3, 6, and 12 months postoperatively. Microperimetry was performed at 12 months postoperatively to evaluate central retinal sensitivity. Regression tree analysis was performed to predict pRNFL thickness at 12 months postoperatively. RESULTS: The temporal quadrant showed continuous pRNFL thinning after surgery, reaching statistical significance at 3, 6, and 12 months postoperatively (all P < 0.001). The pRNFL thicknesses in the fellow eyes significantly increased at all postoperative time points (all P < 0.001). At 12 months postoperatively, the average central retinal sensitivity was significantly correlated with the temporal pRNFL thickness in the eyes with ERM (r = 0.372, P < 0.001); no significant correlation was found in the fellow eyes. Regression tree analysis showed that the preoperative pRNFL thickness in the temporal quadrant and patient age were the main determinants of the temporal pRNFL thickness at 12 months postoperatively. CONCLUSIONS: The risk of deterioration of central retinal sensitivity after ERM vitrectomy with internal limiting membrane peeling should be considered for patients with thin temporal pRNFLs and older adults.

Microdosimetric Modeling of Relative Biological Effectiveness for Skin Reactions: Possible Linkage Between In Vitro and In Vivo Data.

PURPOSE: Precise evaluation of the relative biological effectiveness (RBE) for skin reactions is indispensable for the treatment planning of particle therapy and boron-neutron capture therapy. The evaluation is also needed for the future radiation protection system for mixed radiation fields. Such RBE is often evaluated based on in vitro cell survival data, but its validity remains incompletely understood. This study aimed to develop a model for estimating RBE for skin reactions and dermal cell survival in the same framework and quantitatively discuss a possible link between them. METHODS AND MATERIALS: The microdosimetric kinetic model, which was originally developed for estimating cell surviving fractions for various radiations, was improved to be capable of estimating the mean and uncertainty of RBE for skin reactions. The parameter used in the model was independently determined from in vitro measurements of dermal cell survival and in vivo measurements of skin reactions taken from 8 and 23 articles, respectively. In the parameter determination, the characteristics of the radiation fields employed in each measurement were reproduced in detail by the Particle and Heavy Ion Transport Code System. RESULTS: Our model quantitatively revealed that RBE for skin reactions tend to be higher than those for dermal cell survival. RBE of various monoenergetic radiations calculated from this model confirmed that the past evaluations made by the International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements a few decades ago are still supported by recent experimental data. CONCLUSIONS: Our model can play important roles not only in medical physics for avoiding unnecessary skin reactions in particle therapy and boron-neutron capture therapy but also in radiation protection for future decision-making of the recommended RBE values.

Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle.

Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.