MV X-ray Irradiation Research Articles

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Evaluation of efficacy of tumor-specific nanoliposomal radiosensitizer in radiotherapy

Radiotherapy is one of the cancer treatment options in which ionizing radiation is used. While the ionizing radiation used here damages the tumor cells, it also damages the surrounding healthy cells and tissues. One of the approaches used to reduce the undesirable side effects and increase the therapeutic efficacy of radiotherapy is the use of radiosensitizers. Up to now, different radiosensitizers have been investigated for this purpose and recently, nanotechnology-based radiosensitizer research has attracted much attention. In this study, the therapeutic efficacy of tumor-targeted, nano-sized liposomal radiosensitizers containing quantum dots-photosensitizer conjugate was evaluated in vivo. It was aimed to destroy more tumor cells by using same the radiation doses routinely used in cancer treatment in radiation oncology clinics or to destroy about the same amount of tumor cells by using lower radiation doses than the routinely used clinical dose. For this purpose, nano-sized, PEG-coated, and folic acid-modified tumor-specific liposomes loaded with quantum dots (QD = CdSe/ZnS) - photosensitizer (Ce6 = Clorine-e6) conjugate was prepared and their therapeutic efficacy was evaluated in 4T1 murine breast cancer cell tumor-bearing mice. Following the single dose of 10Gy 6 MV X-ray irradiation after administration of liposomal radiosensitizer, changes in animals' weights and tumor volumes were measured and animal survival was monitored to evaluate the efficacy of the treatment. Histopathological studies were also performed to examine possible damage to the tumor and normal tissues. In control groups, only X-ray irradiation was applied or no treatment was applied to mice. The results showed that the liposomal radiosensitizer plus radiotherapy killed more cancer cells than radiotherapy alone. While tumor volumes increased in the control group, approximately a 39% reduction in tumor volumes was observed in mice treated with x-ray irradiation following administration of the liposomal radiosensitizer. The obtained results showed that nano-sized liposomal radiosensitizers could be a promising radiosensitizer to achieve better treatment efficacy in radiotherapy by applying fewer radiation doses compared to clinically used radiation doses.

Radiation enhancement for kV and MV X-ray irradiation of breast cancer cells incubated with gold nanoparticles

Radiation enhancement for kV and MV X-ray irradiation of breast cancer cells incubated with gold nanoparticles

Role of phosphatidylinositol 3-kinase signaling pathway in radiation-induced liver injury.

Transforming growth factor-β1 (TGF-β1) is one of critical cytokines in radiation-induced liver injury. Hepatic stellate cells (HSC) are activated in the early stage of radiation-induced liver injury. However, it is currently unclear whether phosphatidylinositol 3-kinase (PI3K/Akt) signal pathway is activated in radiation-induced liver injury. Herein, male Sprague-Dawley rats were irradiated with 6 MV X-rays (30 Gy) on the right liver. Next, Hematoxylin and eosin staining, Masson staining, and electron microscopy were performed to examine pathological changes. Immunohistochemistry was performed to assess the expression of TGF-β1, α-SMA, and p-Akt (S473) in liver tissues. In vitro, rat HSC cell line HSC-T6 cells were given different doses of 6 MV X-ray irradiation (10 and 20 Gy) and treated with LY294002. The expression of α-SMA and p-Akt in mRNA and protein levels were measured by reverse transcription-polymerase chain reactioin (RT-PCR) and Western blot. TGF-β1 expression was detected by enzyme-linked immuno sorbent assay (ELISA). After irradiation, the liver tissues showed obvious pathological changes, indicating the establishment of the radiation-induced liver injury. Expression levels of TGF-β1, α-SMA, and p-Akt (S473) protein in liver tissues were significantly increased after irradiation, and this increase was in a time-dependent manner, suggesting the activation of HSC and PI3K/Akt signal pathway. in vitro experiments showed that the TGF-β1 secreted by HSCs, and the expression of Akt and α-SMA at mRNA and protein levels were significantly increased in irradiation groups. However, the expression of TGF-β1, Akt, and α-SMA were significantly decreased in PI3K/Akt signal pathway inhibitor LY294002-treated group. Our results suggest that during radiation-induced liver injury, HSCs are activated by TGF-β1-mediated PI3K/Akt signal pathway.

A capacitor dosimeter with disposable silicon-diode substrates for 4-MV X-ray beam detection in radiation therapy

To monitor patient-surface dose in intensity-modulated radiation therapy (IMRT), developed a novel capacitor dosimeter with a disposable USB-A mini-substrate consisting of a 0.22 ​μF capacitor and a silicon X-ray diode (Si-XD). The capacitor dosimeter consisted of a USB-A mini-substrate and a microcomputer dock. The capacitor in the substrate was charged to 3.30 ​V using the dock before 4 ​MV X-ray irradiation. The charging voltage was reduced by photocurrents flowing through the Si-XD during irradiation. After which the substrate was re-inserted into the dock, and the discharging voltage was measured. A Farmer-type ionization chamber (N30013, PTW) was used to convert the discharging voltages into absorbed dose (Gy). The IMRT study was performed using a custom-made head-neck phantom. The decrease in the charging voltage was found to be proportional to the X-ray dose, and the calibrated dose corresponded well to those obtained using the ionization chamber. The surface dose measured on the head-neck phantom were equivalent to those obtained from a treatment planning system. An inexpensive dosimeter with Si-XDs was developed, as a promising too. The results suggest for monitoring patient-surface dose during radiation therapy.

Evaluation of the Effects of Curcumin and Lycopene Treatment on Human Lymphocytes before 2 and 6 Gy of 6 MV X-Ray Irradiation

Introduction: Today, the use of ionizing radiation in medicine has grown as an important tool for diagnosis and treatment of diseases. However, the harmful effects of radiation should be also considered. Some substances such as lycopene and curcumin can reduce or increase the harmful effects of radiation on humans. So the aim of this study was to evaluate the radioprotective effects of lycopene and curcumin based on the MN assay. Material and Methods: In this study, the effects of lycopene and curcumin on reducing or increasing the harmful effects of radiation were studied using the micronucleus assay. The effects of lycopene (5 μg/mL) and curcumin (5 μg/mL) were evaluated at radiation doses of 2 and 6 Gy. Results: The results indicated that the simultaneous use of curcumin and lycopene can be radioprotective at low radiation doses (2 Gy; p 0.05). Conclusion: Based on the present results, further research using other methods may contribute to our understanding of the effect of simultaneous use of curcumin and lycopene at low and high doses of X-ray radiation.

The Effect of PEI-Mediated E1A on the Radiosensitivity of Hepatic Carcinoma Cells.

Objective:The study was undertaken to investigate the effects of polyethyleneimine (PEI)-mediated adenovirus 5 early region 1A (E1A) on radiosensitivity of human hepatic carcinoma cell in vitro and to disclosure the underlying mechanism. Materials and Methods:Human hepatic carcinoma SMMC-7721 cell line was transfected with E1A gene using PEI vector. Untransfected cells (SMMC-7721 group), cells transfected with blank-vector (SMMC-7721-vect group), and cells transfected with E1A gene (SMMC-7721-E1A group) were treated with 6 MV X-ray irradiation at doses of 0, 1, 2, 4, 8 and Gy, respectively. Radiosensitivity was determined by MTT assay and quantified by calculating the cell survival rate. Cell-cycle distribution and apotosis rate were monitored by flow cytometry. Results:The survival rate of SMMC-7721-E1A was significantly lower than that of SMMC-7721 cell. Apoptosis rate of SMMC-7721-E1A group was significantly higher than that of SMMC-7721group (P<0.01).The ratio of S stage in cell cycle of SMMC-7721-E1A was significantly lower than that in SMMC-7721 cell. The ratio of G2/M stage in cell cycle of SMMC-7721-E1A was significantly higher than that in SMMC-7721 cell (P<0.01). Conclusion:PEI could transfect E1A gene into hepatic carcinoma cells PEI-mediated E1A could effectively enhance radiosensitivity of hepatic carcinoma cells which may be related to its effects on apoptosis promoting leading to S phase suppression and G2/M phase arrest.

Experimental investigation of radiobiology in head and neck cancer cell lines as a function of HPV status, by MTT assay

Head and neck cancers (HNCs) are aggressive epithelial tumours frequently treated using radiation. HNC biology shows distinctions dependent on the oncologic involvement of the human papilloma virus (HPV). Clinically, HPV positive HNCs respond better to radiotherapy but few in vitro data demonstrate radiobiological differences explaining differences in clinical outcomes. This pilot study examined radiobiological responses to irradiation and subsequent regeneration in two HNC cell lines (HPV positive and negative). A novel approach was taken to develop generational cultures of HNC cell lines, UM-SCC-1 (HPV negative) and UM-SCC-47 (HPV positive). MTT assays were used to determine surviving metabolic activity as a function of dose following 6 MV X-ray irradiation. Parallel cultures surviving 4 Gy irradiation (not analysed) were re-cultured and passaged to develop subsequent generations which were re-irradiated and analysed for generational change in radiation response. Second and 3rd generations of UM-SCC-1 showed decreasing metabolic activity with dose but little difference was evident in surviving fractions between these generations. Significantly lower metabolic activity in the 3rd generation at <6 Gy, compared to the 2nd generation, showed UM-SCC-47 becoming progressively more radiosensitive. HPV positive UM-SCC-47 showed generational progression in radiosensitisation not seen in the HPV negative UM-SCC-1.

Radiosensitisation enhancement effect of BrUdR and Ta2O5 NSPs in combination with 5-Fluorouracil antimetabolite in kilovoltage and megavoltage radiation

This article demonstrates in vitro a synergistic effect on 9L gliosarcoma cells when exposed to bromodeoxyuridine (BrUdR) and a low concentration (100 times lower than the IC50) of 5-Fluorouracil (5-FU), in combination with x-ray irradiation. The synergy is brought about by several important factors including the x-ray beam energy, atomic number of the BrUdR (Z = 35), effectiveness of 5-FU in reducing the available repair processes and distribution of the BrUdR in and around the 9L cells (32% of the total substitution of BrUdR for thymidine into nucleus DNA). Our results show that the synergistic effect, evident in an optimised 125 kVp x-ray field, leads to a radiosensitisation enhancement ratio at the 10% survival level (SER10%) of 2.11. We highlight the importance of the aforementioned factors by similarly performed experiments for higher Z (Z = 73) tantalum pentoxide nano-structured particles (Ta2O5 NSPs) that are substituted for the BrUdR in larger concentration (∼10 times). In the Ta2O5 NSPs experiments, no synergistic effect is observed in the kVp irradiation with optimal energy spectrum even though the effective Z and NSP concentration is much higher than for BrUdR. All experiments were repeated using a MV x-ray irradiation field and no synergistic effect is observed for either the BrUdR or Ta2O5 case. We therefore hypothesise that the synergistic outcome is due to more drastic and complex damages induced by BrUdR under the exposure of kVp radiation. Such damages are achieved by the localisation of the BrUdR in the DNA and the high LET (very short range) secondary electrons in combination with the 5-FU. In order to achieve similar synergistic effects in the more clinically relevant x-ray energy field the concentration of the high Z material needs to be greater in order to create a higher LET electron environment.

Effect of E1A gene on radiosensitivity of human nasopharyngeal carcinoma cells and its possible mechanism

Objective To investigate the effect of E1A gene on the radiosensitivity of human nasopharyngeal carcinoma cells and its possible mechanism. Methods The E1A gene was transfected into nasopharyngeal carcinoma CNE-2R cells by adenovirus vector. The expression of E1A gene was detected by RT-PCR. Untransfected CNE-2R cells (PBS group) and CNE-2R cells transfected with empty vector Ad-β-gal (Ad-β-gal group) and E1A (Ad-E1A group) were given 0 Gy, 2 Gy, 4 Gy, 6 Gy, 8 Gy 6 MV X-ray irradiation. The changes in radiosensitivity of CNE-2R cells were determined by colony-forming assay. Flow cytometry was used to analyze cell apoptosis in each group. The expression of NF-κB, CK2α, Bcl-2, and cleaved caspase-3 was measured by Western blot. Results RT-PCR confirmed that the E1A gene was transfected into CNE-2R cells and stably expressed. The Ad-E1A group had a significantly lower plating efficiency than the PBS group and the Ad-β-gal group (P<0.05). The Ad-E1A group had significantly lower cell survival rate at 2 Gy irradiation than the PBS group and the Ad-β-gal group (0.217 vs. 0.602, P<0.05; 0.217 vs. 0.585, P<0.05). The Ad-E1A group had a significantly higher α/β value than the PBS group and the Ad-β-gal group (24.680 vs. 5.268, P<0.05; 24.680 vs. 5.132, P<0.05). Flow cytometry results showed that irradiation alone could promote the apoptosis of CNE-2R cells, when combined with E1A gene, the apoptosis rate was significantly increased (P<0.05). Western blot results showed that E1A gene down-regulated the expression of NF-κB/p65, CK2α, and Bcl-2 and up-regulated the expression of cleaved caspase-3. Conclusions E1A gene can enhance the radiosensitivity of nasopharyngeal carcinoma cells by inhibiting the expression of CK2 to block the NF-κB signaling pathway and promoting cell apoptosis. Key words: E1A gene; NF-κB; Casein Kinase 2; Nasopharyngeal Carcinoma Cell; Radiosensitivity; Apoptosis

Effect of Ku80 on the radiosensitization of cisplatin in the cervical carcinoma cell line HeLa.

Cisplatin chemotherapy in combination with radiotherapy is the primary therapeutic strategy for the treatment of cervical cancer; however, the underlying molecular mechanism for cisplatin radiosensitization remains unknown. The aim of the present study was to investigate the effect of Ku80, a DNA double-strand break (DSB) repair protein, on cisplatin radiosensitization in cervical cancer. The pre-established Ku80 suppression cervical cancer cell line HeLa/Ku80-siRNA and the normal HeLa cell line underwent 6 MV X-ray irradiation (6 Gy) individually or in combination with 5 µg/ml cisplatin treatment. Alterations in apoptosis, the cell cycle and γH2AX expression were detected. Following irradiation individually and combined with cisplatin, compared with normal HeLa cells, HeLa/Ku80-siRNAexhibited an increased rate of apoptosis (P<0.05). It was identified that the earlier cisplatin was administered following irradiation, the higher the rate of apoptosis. Cell cycle analysis indicated that, following irradiation combined with cisplatin, the cells were arrested in G1 and S phase rather than in G2/M phase following irradiation alone. Microscopic imaging of immunofluorescence staining and western blotting identified that HeLa/Ku80-siRNA cells exhibited more γH2AX foci remaining following treatment with irradiation and cisplatin, particularly in the group treated with 6 Gy irradiation for 1 h together with 23 h of exposure to cisplatin. Irradiation in combination with cisplatin promoted the apoptosis of HeLa cells in association with the inhibition of Ku80, and it was identified that the earlier cisplatin was administered following irradiation, the more apoptosis was induced. This maybe because irradiation combined with cisplatin is able to arrest cells in G1 and S phase to rapidly repair damaged DNA, and the lack of Ku80 induces the inability to repair DSB, resulting in increased apoptosis. The results of the present study suggest that Ku80 may be a potent molecular target in cisplatin radiosensitization.

Micronuclei Assessment of The Radioprotective Effects of Melatonin and Vitamin C in Human Lymphocytes.

Critical macromolecules such as DNA maybe damaged by free radicals that are generated from the interaction of ionizing radiation with biological systems. Melatonin and vitamin C have been shown to be direct free radical scavengers. The aim of this study was to investigate the in vivo/in vitro radioprotective effects of melatonin and vitamin C separately and combined against genotoxicity induced by 6 MV x-ray irradiation in human cultured blood lymphocytes. In this experimental study, fifteen volunteers were divided into three groups of melatonin, vitamin C and melatonin plus vitamin C treatment. Peripheral blood samples were collected from each group before, and 1, 2 and 3 hours after melatonin and vitamin C administration (separately and combined). The blood samples were then irradiated with 200 cGy of 6 MV x-ray. In order to characterize chromosomal aberrations, the lymphocyte samples were cultured with mitogenic stimulus on cytokinesisblocked binucleated cells. The samples collected 1hour after melatonin and vitamin C (separately and combined) ingestion exhibited a significant decrease in the incidence of micronuclei compared with their control group (P<0.05). The maximum synergic protection and reduction in frequency of micronuclei (57%) was observed 1 hour after vitamin C and melatonin administration combined. We conclude that simultaneous administration of melatonin and vitamin C as radioprotector substances before irradiation may reduce genotoxicity caused by x-ray irradiation.

Effect of single high-dose irradiation on rat hepatic stellate cells, transforming growth factor β, and PI3K/Akt signaling pathway molecule p-Akt (S473)

Objective To investigate the effect of single high-dose irradiation on rat hepatic stellate cells (HSCs), transforming growth factor β(TGF-β), and PI3K/Akt signaling pathway. Methods A total of 40 healthy male Sprague-Dawley rats were randomly divided into model group (30 rats) and control group (10 rats). The rats in the model group were given single 6 MV X-ray irradiation of the right liver at a dose of 30 Gy, and those in the control group were given sham irradiation with the same method. At 3, 5, and 10 days after irradiation, 10 rats in the model group and 3-4 rats in the control group were randomly selected to measure the changes in the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALP), alkaline phosphatase (ALP), total bilirubin (TB), and direct bilirubin (DB). Hematoxylin-eosin (HE) staining and Masson staining were applied for liver tissues to observe the pathomorphological changes, and immunohistochemistry was used to measure the expression of transforming growth factor-beta 1(TGF-β1), alpha-smooth muscle actin (α-SMA), and p-Akt (S473) in liver tissues. Results At 3, 5, and 10 days after irradiation, the model group showed increases in the serum levels of AST, ALT, ALP, TB, and DB, and had significantly higher serum levels of these indices than the control group. The HE staining and Masson staining showed that compared with the control group, the rats with acute liver injury induced by radiation in the model group had a significant formation of collagen fibers around the hepatic sinusoids. Immunohistochemistry showed that with the prolonged time after irradiation, the expression of TGF-β1, α-SMA, and p-Akt (S473) was gradually enhanced after irradiation, and IPP analysis showed significant differences between the two groups (P<0.000). Conclusions During the process of acute radiation-induced liver injury induced by single high-dose irradiation, with the activation of HSCs, the secretion of TGF-β1 is increased and the PI3K/Akt signaling pathway is activated. Key words: Radiation induced liv er injury; Transforming growth factor beta; Hepatic stellate cells; Signal pathway

Thermoluminescence Properties of Optical Fibers Doped with RE&lt;sup&gt;+3&lt;/sup&gt; (RE=Sm, Nd) Ions Subjected to X-Ray Irradiation

This paper describes the thermoluminescence properties of RE+3(RE=Nd, Sm) doped optical fiber SiO2 prepared by CorActive company in Canada. The samples were exposed to 6 MV X-ray irradiation at dose ranging from 0.5 to 4 Gy at hospital Sultan Ismail, Johor Bahru, Malaysia using the LINAC accelerator. After exposure and a certain delay of 12 h to get uniform control of thermal fading, the optical fiber TL yield was readout using a TL reader. The optical fiber demonstrated a linear TL response versus of the absorbed dose. The linearity increases with the increasing dose while in the case of Sm-doped optical fiber; the response is comparatively smaller than Nd-doped optical fiber. Also, the glow curve of RE+3 ions doped optical fiber is compared with the undoped fibers. The results exhibit that the glow curve peaks are shifted to higher temperature due to rare-earth doping. As the results indicate the TL response strongly depends on the doping type of materials. All these TL characteristics are proposing this commercial optical fiber very decisive TL material.

The effect of 100 Hz magnetic field combined with X-ray on hepatoma-implanted mice

Our previous cellular experiments demonstrated that 100 Hz magnetic field (MF) was effective at enhancing apoptosis of liver cancer cells BEL-7402 induced by X-ray irradiation. This study was performed to further explore the possible synergism between 100 Hz MF and X-ray in treatment of hepatoma-implanted Balb/c mice. 100 Hz MF exposure with a mean flux density of 0.7 mT was performed inside an energized solenoid coil. Six MV X-ray irradiation was generated using a linear accelerator. Tumor growth and survival of mice implanted with H22 cells were evaluated by measuring the tumor diameters and overall days of survival. Six groups treated with 100 Hz MF or X-ray alone or a combination of MF and X-ray were examined. Furthermore, the effects of different numbers of MF exposure periods on tumor growth and mice survival were examined when combined with 4 Gy X-ray. Data referring to overall survival days and tumor diameters of the above groups were compared using log-rank test and Student's t-test. Our results showed that five periods of combined 100 Hz MFs and 4 Gy X-ray could significantly extend the overall days of survival and reduce the tumor size compared to MF or X-ray alone. Also, a greater number of 100 Hz MF exposure periods could further improve the survival and inhibit tumor growth in hepatoma-implanted mice when combined with 4 Gy X-ray. In conclusion, these findings suggested that 100 Hz MF could possibly synergize with 4 Gy X-ray in terms of survival improvement and tumor inhibition in hepatoma-implanted mice.

Radiation-induced sarcoma in bronchial stump after thoracic radiation therapy for small-cell lung cancer

We report a rare case of radiation-induced sarcoma (RIS) that arose in the right bronchial stump, 8 years after right pneumonectomy followed by adjuvant chemotherapy and thoracic radiotherapy for a localized small-cell lung cancer. The patient was treated in 2002 with 6 MV X-ray irradiation in a total dose of 60 Gy. Eight years after the end of radiotherapy, he presented with an undifferentiated high-grade pleomorphic sarcoma. Although an increased rate of soft tissue sarcoma has been reported after radiotherapy for some solid cancers or lymphomas, to our knowledge, this is the first report of RIS related to small-cell lung cancer.

Radiation-induced reactive oxygen species formation prior to oxidative DNA damage in human peripheral T cells

Previously, we demonstrated that human peripheral T lymphocytes revealed early apoptotic changes (annexin V-positive) and late apoptotic changes (propidium iodide-positive), at 13 and 24 h, respectively, after irradiation of 5 Gy. Changes in mitochondrial membrane potential were observed at 10 h after irradiation of 5 Gy. Subsequently, mitochondrial cytochrome c-release was confirmed. In order to elucidate the mechanism which acts prior to the mitochondrial membrane potential changes, we examined in the previous study the radiation dose and the timing of oxidative DNA damage induced in human peripheral T lymphocytes following 10 MV X-ray irradiation. As a result, the production of 8-oxoguanine, i.e., the product of oxidative DNA damage, was clearly identified starting at 10, 6, and 3 h, after 2, 5, and 20 Gy of irradiation, respectively. Therefore, we examined in the present study reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy of irradiation. Using a CCD camera system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl ester of dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent until oxidized by ROS. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation.

Radiation-induced oxidative DNA damage, 8-oxoguanine, in human peripheral T cells

The mechanism leading to the high level of radiosensitivity of T lymphocytes has not yet been fully described. In our previous study, we demonstrated that human peripheral T lymphocytes revealed early apoptotic changes (annexin V-positive) and late apoptotic changes (propidium iodide-positive), at 13 and 24 h after irradiation of 5 Gy, respectively. Changes in mitochondrial membrane potential were observed at 10 h after irradiation of 5 Gy. Subsequently, mitochondrial cytochrome c release was confirmed. In order to elucidate the mechanism which occurs prior to the mitochondrial membrane potential changes, we examined in the present study the radiation dose and the timing of oxidative DNA damage induced in human peripheral T lymphocytes following 10 MV X-ray irradiation. As a result, the production of 8-oxoguanine, i.e., the product of oxidative DNA damage, was clearly identified starting at 10, 6, and 3 h, after 2, 5, and 20 Gy of irradiation, respectively. Therefore, we concluded that it remains necessary to evaluate the extent of radiation-induced oxidative DNA damage. Furthermore, it is important to analyze superoxide radical production and scavenging in terms of the variety of radiosensitivities found among various types of normal tissue cells and neoplastic cells.

Measurement of the response of Gd2O2S:Tb phosphor to 6 MVx-rays

The phosphor Gd2O2S:Tb is widely used in camera-based electronicportal imaging devices (EPIDs). There is considerable interest in theapplication of EPIDs to dosimetry and the verification of intensitymodulated radiation therapy produced by dynamic multileaf collimation(DMLC). This paper presents direct measurement of Gd2O2S:Tb phosphorluminescence under 6 MV x-ray irradiation from a linear accelerator using aphotomultiplier tube. The luminescence following each radiation pulse(3 µs duration) was observed to decay with a dominant lifetime of558 µs. Using a specialized electrometer, the temporal variation of theoptical signal has been compared with the dose rate incident on thephosphor measured using a semiconductor diode detector. Under dose ratestypical of those used in the clinic (1.2 Gy min -1 to thephosphor), measurements at beam-start confirmed that the optical signal islinear with dose per radiation pulse. Measurements at beam terminationfollowing phosphor doses up to 4.4 Gy showed no residual signal associatedwith long-lived luminescence (afterglow) from the phosphor above the noiselevel of the optical signal (0.17% standard deviation). This measurementdemonstrates that afterglow from Gd2O2S:Tb is not of significance forits application to DMLC verification. Additionally, it was confirmed thatthe accelerator pulse repetition frequency has no effect on the opticalsignal from the phosphor in the range 25-400 Hz.

Relative biological effectiveness of the 235 MeV proton beams at the National Cancer Center Hospital East.

A therapy-dedicated cyclotron was installed in the National Cancer Center Hospital East (NCCHE) at Kashiwa in 1997. Prior to the start of clinical use, we investigated the biological effectiveness of therapeutic proton beams for cell lethality. The proton beams accelerated up to 235 MeV were horizontally extracted from the cyclotron, and scattered by a bar-ridge filter to produce a Spread-Out-Bragg-Peak (SOBP) of 10-cm width. The biological systems used here were mouse intestinal crypt cells and three in vitro cell lines, including SCC61 human squamous cell carcinoma, NB1RGB human fibroblasts and V79 Chinese hamster cells. The dose responses after irradiation at either the entrance plateau or the middle portion of SOBP were compared with those after linac 6 MV X-ray irradiation. The fit of a linear quadratic model to survival curves showed that proton irradiation increased the alpha value of SCC61 and the beta value of V79 cells with a least change for alpha/beta ratio of NB1RGB cells. The isoeffect dose that reduces either cell survivals to 10% or mouse jejunum crypts to 10 per circumference was termed D10. The relative biological effectiveness (RBE) of protons obtained by comparing the D10 values between protons and X-rays ranged from 0.9 to 1.2. The depth distribution of cell lethality was measured by replating V79 cells after irradiation from a "cell stack chamber" that received a single dose of 7 Gy at the middle position of SOBP. The thus-obtained cell survivals at various depths coincided well with the estimated survivals, but tended to decrease at the distal end of SOBP. We conclude that an RBE of 1.1 would be appropriate for 235 MeV proton beams at the NCCHE.