Design of a novel nanoparticle to use X-ray fluorescence of TiO2 to induce photodynamic effects in the presence of PpIX.

BACKGROUND: Radiotherapy and photodynamic therapy are the methods of cancer treatment. Although one limitation of photodynamic therapy (PDT) is the limited penetration depth of light through tissue, using X-rays does not have this restriction. Self-lighting nanoparticles can convert X-rays into UV/visible. This study focuses on a newly designed nanostructure containing mesoporous silica nanoparticles (MSN), titanium dioxide nanoparticles (TiO2, anatase grade), and protoporphyrin IX (PpIX) as a photosensitizer to overcome the limitations of photodynamic therapy. METHODS: After the synthesis and characterization of Ti-MSN/PpIX@PVP nanostructure, two ROSes (OH* and 1O2) were measured when the nanostructures were irradiated with 100 kV and 6 MV photons. The toxicity of Ti-MSN/PpIX@PVP nanostructure in presence and absence of radiation was investigated on DFW and HT-29 cell lines. The in-vitro experiments were analyzed using the MTT assay and colony count assay. Finally, the effect of light exposure in the presence of Ti-MSN/PpIX@PVP nanostructure on the two cell lines was studied. The in-vitro studies were evaluated using the Synergism Index (Syn) and Dose Enhancement Factor (DEF). RESULTS: Based on the FESEM (field emission scanning electron Microscopy) images and DLS (dynamic light scattering) measurements, the size of Ti-MSN/PpIX nanostructure was determined as (35.2 nm) and (168.4 nm), respectively. Based on the spectrofluorimetry results, 100 kV photons produced more ROSes than 6 MV photons. The results of MTT assay and colony formation for X-PDT show Syn >1, except for 100 kV photons for HT-29 cell line. The nanostructure also reduced colony formation induced by X-PDT more effectively when irradiated by 100 kV photons on DFW cells. The results obtained from conventional PDT showed that the ED 50 of the HT-29 cell line was 6 times higher than that of the DFW cell line. CONCLUSION: Designing and synthesizing Ti-MSN/PpIX@PVP nanostructures offer a promising strategy for reducing the current challenges in PDT and for developing and advancing X-PDT as an innovative cancer treatment technique.

Preliminary Results of the Effects of Localized High-Dose Radiotherapy Combined with Total Body Low-Dose Irradiation on Tumor Growth and Stimulating the Immune System in Tumor-Bearing Mice.

Background: The immune system plays an extensive role in eliminating tumor cells. On the other hand, low-dose irradiation stimulates the immune system. Objective: The present study aimed to investigate the therapeutic outcomes of localized high-dose radiotherapy (LH) alone and combined with total body low-dose irradiation (TB). Material and Methods: In this experimental study, B16F0 tumor cells were injected into the right flank of C57JL/6 mice. The mice were treated with LH alone (13 Gy X-rays to the tumor surface) (LH group) or combined with TB (85 mGy X-rays at the skin) (TB+LH group). Then the tumor volume, the mice's lifespan, the number of lymphocytes extracted from the spleen, and interferon gamma (IFN-γ) production were measured. Results: Reduced number of lymphocytes, compared to non-irradiated mice (control group), was observed in LH and TB+LH groups. However, the identical number of cultured lymphocytes produced a higher level of IFN-γ in irradiated groups. Comparing the irradiated groups, the number of lymphocytes and their IFN-γ production, tumor growth control, and the mice's lifespan were statistically higher in TB+LH group. Conclusion: Observing a higher level of IFN-γ in TB+LH group compared to LH group indicates that low-dose radiation enhanced the stimulating effects of high-dose radiation on the immune system. It caused the mice in TB+LH group to have a more prolonged lifespan and a lower tumor growth rate. Therefore, it is worth our attention for future studies to investigate whether total body low-dose irradiation can be utilized before radiotherapy to enhance its efficiency.

High-dose Irradiation Stimulated Breast Tumor Microenvironment to Enhance Tumor Cell Growth and Decrease Tumor Cell Motility.

Background: Surgery and radiotherapy are two main modalities of breast cancer treatment. However, surgery affects the tumor microenvironment negatively and promotes the growth of possible malignant cells remaining in the tumor bed. Objective: The present study aimed to investigate the effects of intraoperative radiotherapy (IORT) on the tumor microenvironment. Therefore, the effect of surgical wound fluid (WF), collected from operated and irradiated patients on the growth and motility of a breast cancer cell line (MCF-7) was assessed. Material and Methods: In this experimental study, preoperative blood serum (PS) and secreted WF from 18 patients who underwent breast-conserving surgery (IORT-) and 19 patients who received IORT following surgery (IORT+) were collected. The samples were purified and added to MCF-7 cultures. Two groups of the cells were treated with and without fetal bovine serum (FBS) and used as positive and negative controls. Applying 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch wound healing assays, the growth and motility of MCF-7 cells were measured. Results: Cell growth of the cells receiving WF from IORT+ patients (WF+) was statistically higher than the corresponding values of the cells received PS or WF from IORT- patients (WF-) (P<0.01). Both WF+ and WF- decreased the cells' migration ability compared to PS (P<0.02) and FBS (P<0.002), although WF+ caused a more significant reduction (P<0.02). Conclusion: Wound fluid extracted from breast cancer patients who underwent both surgery and IORT increased the growth of breast tumor cells, but decreased their ability to migrate.

Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement.

AIMS: In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams. MATERIALS AND METHODS: The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system. RESULTS: OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2. CONCLUSIONS: The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam.

Regulation of XPA could play a role in inhibition of radiation-induced bystander effects in QU-DB cells at high doses.

INTRODUCTION: Radiation-induced bystander effects (RIBE) is the radiobiological effects detected in nonirradiated cells that have received signals from neighboring irradiated cells. In some studies, there are observations that RIBE unexpectedly reduces at high doses. In this study, the expression of two selected apoptotic and repair genes and their possible role in the formation of this unexpected reduction is examined. MATERIALS AND METHODS: The QU-DB cells were irradiated with gamma rays of a60 Co teletherapy unit at doses of 2, 4, 6, and 8 Gy. One hour following irradiation, their culture media were transferred to bystander cells to induced RIBE. After 24 h incubation, the RNA of cells was isolated and cDNA synthesized. Expression levels of BAX, XPA, and XPA/BAX ratio were examined by relative quantitative reverse transcription-polymerase chain reaction. RESULTS: In target cells, up-regulation of both genes was observed at all doses. In bystander cells, at the low dose (2 Gy), the expression of BAX was more than XPA; at 4 Gy, the ratio was balanced. A significant correlation was found between the XPA/BAX ratio and the dose, at high doses pattern of gene expression dominated by DNA repair gene. CONCLUSION: Gene expression profile was distinctive in bystander cells compared to target cells. The observed linear increasing of the ratio of XPA/BAX could support the hypothesis that the DNA repair system is stimulated and causes a reduction in RIBE at high doses.

Coadministration of auraptene and radiotherapy; a novel modality against colon carcinoma cells in vitro and in vivo.

Background: Use of ionizing radiation (IR) is a common therapeutic modality for patients with colon carcinoma, although resistance of cancer cells and unintended toxicity reduce clinical outcomes.Purpose: To enhance radioresponse of colon cancer cells, we designed a novel approach using auraptene (AUR) in combination with ionizing radiation (IR).Methods: For in vitro studies, CT26 cells were pretreated with AUR and irradiated at different doses. Then, cell viability was evaluated by alamarBlue assay, and the mechanism of cell death was elucidated using annexin V-PI. To determine efficacy of our combined therapeutic modality in vivo, AUR was injected intraperitoneally to murine models of colon carcinoma followed by IR, and then quantitative measurements and histopathological examinations were performed. For molecular analyses, real time PCR and Western blot were carried out.Results: Assessment of cell viability indicated significant enhancement of IR effects by AUR that was also confirmed by increased number of apoptotic cells. In vivo studies further demonstrated improved outcome in IR, since significant regression in tumor size was observed after administration of AUR + IR. Molecular analyses revealed down regulation of Cyclin D1 and CD44, along with involvement of PI3K-AKT-mTORC signaling pathway and Caspase-3 in observed combinatorial effects.Conclusion: Taken together, current findings support our previous reports on sensitizing effects of AUR and that AUR could be used as a promising adjunct to IR in cancer treatment.

Investigating the Vinblastine Induced-Chromosomal Abnormality in the Already Gamma Irradiated L929 Cell Line Using Micronucleus Assay in Cytokinesis Blocked Binucleated Cells

Objectives: Vast number of studies show the relationship between aneuploidy and cancer. Ionizing radiation in addition to induce all kinds of damages to the cells and structure of chromosomes, is also able to induce aneuploidy through direct damages to chromosome division apparatus. Also irradiation of the cells induces mutations in several genes which might be involved in cell division fidelity and play a role in reversing the effect of aneugens. Therefore, irradiation of cells and tissues might produce sensitivity to agents with aneugenic capability in irradiated cells. Methods: To investigate the persistent genomic effect of ionizing irradiation on chromosomal instability, L929 cells were gamma irradiated with the dose of 2 Gy. Cells were left to recover from the harmful effect of irradiation. They were treated with low dose of vinblastine (0.5 ng.ml-1) 72h post-gamma irradiation. Finally, the induced chromosomal abnormalities were scored using micronucleus assay in cytokinesis-blocked binucleated cells (MnBi). Results: Irradiation-recovered L929 cells treated with vinblastine showed a statistically higher frequency of MnBi compared to non-irradiated and vinblastine treated cells. Conclusion: The results indicate that gamma irradiation, in addition to direct induction of chromosomal damages, is also able to create persisting genomic sensitivity in the cells to chromosomal instability, which is detectable when exposed to the second stimulus.

Correlation between expression of CatSper1,2 and sperm parameters in the gamma irradiated adult mouse testis.

Propose: CatSper protein channels are responsible for the entry of Ca2+ into sperm cells. These proteins play an important role in motility and male fertility. So it is important to find out whether or not environmental factors, such as gamma radiation, have an effect on the expression of Catsper genes. In this study, we investigated the effects of gamma radiation on the expression of CatSper1 and CatSper2 genes. Materials and methods: Twenty-one male NMRI mice were divided into three groups: a control group without gamma radiation, and two experimental groups; Group 1 treated with 1 Gy of gamma radiation, and Group 2 treated with a higher dose of 2 Gy gamma radiation. Testes were removed from all groups of animals 35 days following irradiation and the testicular tissue, processed and embedded in paraffin blocks for sectioning and histological examination. Sperm samples were also taken from the epididymis for microscopic. Sperm parameters such as sperm count, morphology, motility, and viability rates were analyzed. Expression of CatSper genes was evaluated using Real-time PCR. Data were analyzed using the SPSS software and ANOVA test. Results: Our results showed that after treatment with gamma radiation, testes morphology was changed. Epididymal sperm count, motility, and morphology rates were significantly affected in both experimental groups compared to the control group. The relative expressions of CatSper 1 and 2 genes were significantly reduced in the irradiated mice (1 Gy and 2 Gy) than non-irradiated ones. Conclusions: Gamma radiations not only change testes histology and sperm parameters, but also decrease the expression of CatSper 1 and 2 genes in male mice.

Evaluation of electron dose calculations accuracy of a treatment planning system in radiotherapy of breast cancer with photon-electron technique.

AIM: The aim of this study was to assess the accuracy of electron dose calculations of Prowess Panther treatment planning system (TPS) for abutting photon-electron (PE) technique. In this work, we have assessed the accuracy of electron dose calculations in a simulated internal mammary field because this field is irradiated with electron in PE technique. MATERIALS AND METHODS: In this study, regions of in-field, under electron shield, and outside the internal mammary field were evaluated. Thermoluminescent dosimeter (TLD-700) chips were used within RANDO phantom for dose measurement. Prowess Panther TPS was also applied for dose calculation. Finally, confidence limit values were obtained to quantify the TPS electron dose calculation accuracy of an internal mammary field. RESULTS: The results show that for outside of field and under shield regions, Prowess Panther TPS underestimated the dose compared to the measured doses by TLD-700, whereas for in-field regions, the calculated doses by Prowess Panther TPS compared to the measured doses by TLD-700, for some points are overestimated and other points are underestimated. Finally, the confidence limit values were obtained for various regions of the internal mammary field. Confidence limits for in-field, outside of field, and under shield regions were 54.23, 108.19, and 80.51, respectively. CONCLUSIONS: It is concluded that the accuracy of electron dose calculations of Prowess Panther TPS is not adequate for internal mammary field treatment. Therefore, it is recommended that for fields with electron beams Prowess Panther TPS calculations should not be entirely relied upon.

Assessment of accuracy of out-of-field dose calculations by TiGRT treatment planning system in radiotherapy.

AIM: The objective was to quantify the accuracy of dose calculation for out-of-field regions by the commercially available TiGRT version 1.2 (LinaTech, Sunnyvale, CA, USA) treatment planning system (TPS) for a clinical treatment delivered on a Siemens Primus with the single energy of 6 MV. MATERIALS AND METHODS: Two tangential open fields were planned by TiGRT TPS to irradiate the left breast of a RANDO phantom. Dose values to out-of-field points were calculated by TiGRT TPS. A RANDO phantom was then irradiated, and dose values at set points were measured using thermoluminescent detectors-100 (TLDs-100) which were located within the phantom. Finally, the TLD-measured dose was compared to the TPS-calculated dose and the accuracy of TPS calculations at different distances from the field edge was quantified. RESULTS: The measurements showed that TiGRT TPS generally underestimated the dose of out-of-field points and this underestimation worsened for regions relatively close to the treatment field edge. The mean underestimation of out-of-field doses was 39%. Nevertheless, the accuracy of dose calculation by this TPS for most in-field regions was within tolerance. CONCLUSION: This study highlights the limitations of TiGRT TPSs in calculating of the out-of-field dose. It should be noted that out-of-field data for this TPS should only be applied with a certain understanding of the accuracy of calculated dose outside the treatment field. Therefore, using the TPS-calculated dose could lead to an underestimation of secondary cancer risk as well as a weak clinical decision for patients with implantable cardiac pacemakers or pregnant patients.

Assessment of the accuracy of dose calculation in the build-up region of the tangential field of the breast for a radiotherapy treatment planning system.

AIM OF THE STUDY: Our objective was to quantify the accuracy of dose calculation in the build-up region of the tangential field of the breast for a TiGRT treatment planning system (TPS). MATERIAL AND METHODS: Thermoluminescent dosimeter (TLD) chips were arranged in a RANDO phantom for the dose measurement. TiGRT TPS was also used for the dose calculation. Finally, confidence limit values were obtained to quantify the accuracy of the dose calculation of the TPS at the build-up region. RESULTS: In the open field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 17.68, 19.97, and 34.62 at a depth of 5 mm, and 24.01, 19.07, and 15.74 at a depth of 15 mm, respectively. In the wedge field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 21.64, 26.80, and 34.87 at a depth of 5 mm, and 27.92, 22.04, and 20.03 at a depth of 15 mm, respectively. Additionally, the findings showed that at a depth of 5 mm, the confidence limit values increased with increasing gantry angle while at a depth of 15 mm, the confidence limit values decreased with increasing gantry angle. CONCLUSIONS: Overall, TiGRT TPS overestimated doses compared to TLD measurements, and the confidence limit values were greater for the wedge field than for the open fields. Our findings suggest that the assessment of dose distributions in large-dose gradient regions (i.e. build-up region) should not entirely rely on TPS calculations.

Automatic detection of micronuclei by cell microscopic image processing.

With the development and applications of ionizing radiation in medicine, the radiation effects on human health get more and more attention. Ionizing radiation can lead to various forms of cytogenetic damage, including increased frequencies of micronuclei (MNi) and chromosome abnormalities. The cytokinesis block micronucleus (CBMN) assay is widely used method for measuring MNi to determine chromosome mutations or genome instability in cultured human lymphocytes. The visual scoring of MNi is time-consuming and scorer fatigue can lead to inconsistency. In this work, we designed software for the scoring of in vitro CBMN assay for biomonitoring on Giemsa-stained slides that overcome many previous limitations. Automatic scoring proceeds in four stages as follows. First, overall segmentation of nuclei is done. Then, binucleated (BN) cells are detected. Next, the entire cell is estimated for each BN as it is assumed that there is no detectable cytoplasm. Finally, MNi are detected within each BN cell. The designed Software is even able to detect BN cells with vague cytoplasm and MNi in peripheral blood smear. Our system is tested on a self-provided dataset and is achieved high sensitivities of about 98% and 82% in recognizing BN cells and MNi, respectively. Moreover, in our study less than 1% false positives were observed that makes our system reliable for practical MNi scoring.

Evaluation of dose calculations accuracy of a commercial treatment planning system for the head and neck region in radiotherapy.

AIM: The objective was to quantify dose calculation accuracy of TiGRT TPS for head and neck region in radiotherapy. BACKGROUND: In radiotherapy of head and neck cancers, treatment planning is difficult, due to the complex shape of target volumes and also to spare critical and normal structures. These organs are often very near to the target volumes and have low tolerance to radiation. In this regard, dose calculation accuracy of treatment planning system (TPS) must be high enough. MATERIALS AND METHODS: Thermoluminescent dosimeter-100 (TLD-100) chips were used within RANDO phantom for dose measurement. TiGRT TPS was also applied for dose calculation. Finally, difference between measured doses (Dmeas) and calculated doses (Dcalc) was obtained to quantify the dose calculation accuracy of the TPS at head and neck region. RESULTS: For in-field regions, in some points, the TiGRT TPS overestimated the dose compared to the measurements and for other points underestimated the dose. For outside field regions, the TiGRT TPS underestimated the dose compared to the measurements. For most points, the difference values between Dcalc and Dmeas for the in-field and outside field regions were less than 5% and 40%, respectively. CONCLUSIONS: Due to the sensitive structures to radiation in the head and neck region, the dose calculation accuracy of TPSs should be sufficient. According to the results of this study, it is concluded that the accuracy of dose calculation of TiGRT TPS is enough for in-field and out of field regions.

Assessment of The Dose-Response Relationship of Radiation-Induced Bystander Effect in Two Cell Lines Exposed to High Doses of Ionizing Radiation (6 and 8 Gy).

OBJECTIVES: The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints. MATERIALS AND METHODS: This experimental study used the medium transfer technique to induce RIBE. The cells were divided into two main groups: QU-DB cells which received medium from autologous irradiated cells and MRC5 cells which received medium from irradiated QU-DB cells. Colony, MTT, and micronucleus assays were performed to quantify bystander responses. The medium was diluted and transferred to bystander cells to investigate whether medium dilution could revive the RIBE response that disappeared at a high dose. RESULTS: The RIBE level in QU-DB bystander cells increased in the dose range of 0.5 to 4 Gy, but decreased at 6 and 8 Gy. The Micronucleated cells per 1000 binucleated cells (MNBN) frequency of QU-DB bystander cells which received the most diluted medium from 6 and 8 Gy QU-DB irradiated cells reached the maximum level compared to the MNBN frequency of the cells that received complete medium (P<0.0001). MNBN frequency of MRC5 cells which received the most diluted medium from 4 Gy QU-DB irradiated cells reached the maximum level compared to MNBN frequency of cells that received complete medium (P<0.0001). CONCLUSIONS: Our results showed that RIBE levels decreased at doses above 4 Gy; however, RIBE increased when diluted conditioned medium was transferred to bystander cells. This finding confirmed that a negative feedback mechanism was responsible for the decrease in RIBE response at high doses. Decrease of RIBE at high doses might be used to predict that in radiosurgery, brachytherapy and grid therapy, in which high dose per fraction is applied, normal tissue damage owing to RIBE may decrease.

Synergy between Auraptene, Ionizing Radiation, and Anticancer Drugs in Colon Adenocarcinoma Cells.

Colorectal cancer is a growing health concern with increasing mortality rates, and resistance to anticancer drugs and radiotherapy is a serious drawback in its treatment. Auraptene is a natural prenyloxycoumarin with valuable anticancer effects. The aim of current study was to determine the synergy between auraptene, ionizing radiation, and chemotherapeutic drugs in colon adenocarcinoma cells for the first time. To do so, HT29 cells were treated with combination of auraptene + cisplatin, + doxorubicin, or + vincristine. Furthermore, cells were pretreated with nontoxic auraptene and then exposed to various doses of X-radiation. Assessment of cell viability not only indicated significant (p < 0.05) synergic effects of auraptene and anticancer agents, also revealed more significant (p < 0.01) increase in the toxicity of applied radiations in auraptene pretreated cells. Interesting synergy between auraptene and radiotherapy was then confirmed by morphological alterations, DAPI staining, and flow cytometric analysis of the cell cycle. Moreover, real-time reverse transcription polymerase chain reaction analysis indicated significant (p < 0.01) overexpression of p21, but not GATA6, in auraptene pretreated cells after radiotherapy, and also significant (p < 0.01) down regulation of CD44 and ALDH1 by auraptene. According to present results, auraptene could be considered as an effective natural coumarin to improve the outcome of current chemoradiotherapy options. Copyright © 2017 John Wiley & Sons, Ltd.

Study of Crocin & Radiotherapy-induced Cytotoxicity and Apoptosis in the Head and Neck Cancer (HN-5) Cell Line.

Malignant tumors of head and neck carcinomas are the sixth most common type of cancer. Current systemic therapies for cancer show side effects in normal tissues and short-term efficacy due to drug resistance. Consequently, there is much interest in identifying new drugs for cancer treatment. Crocin (an active ingredient of saffron) has been shown to have cytotoxic effects on cancer cell lines. Chemo radiotherapy is the standard treatment for head and neck cancer. In the present study, the cytotoxic effects, inducing apoptosis and the radiation sensitivity of crocin were evaluated in the head and neck cancer cell line (HN-5). HN-5 cells were cultured in a DMEM medium and incubated with different concentrations of crocin (12.5-1000 µg/mL). They were exposed to 2 Gy γ-rays. Cell viability was quantified by the MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flowcytometry (sub-G1 peak). Crocin decreased cell viability in HN-5 cells in a time and concentration dependent manner. Crocin also induced a sub-G1 peak in the flowcytometery histogram of treated cells compared with the control, suggesting that apoptotic cell death is caused by its toxicity. Crocin was also shown to sensitize cells to radiation-induced toxicity and apoptosis. The simultaneous use of crocin and radiation therefore increases radiation sensitivity and cell death. Thus, after further study crocin can be considered as a potential drug and sensitizer in cancer treatment.

Increased radiotoxicity in two cancerous cell lines irradiated by low and high energy photons in the presence of thio-glucose bound gold nanoparticles.

PURPOSE: Gold nanoparticles modified by thio-glucose are believed to increase the toxicity of radiotherapy in human malignant cells. We report the effect of thio-glucose bound gold nanoparticles (Glu-G nanoparticles), 16 nm in size, on two human lung (QU-DB) and breast (MCF7) cancer cell lines combined with kilo and megavoltage X-rays. MATERIALS AND METHODS: The shape and surface characteristics, the size distribution and light absorption spectrum of the prepared nanoparticles were measured by transmission electron microscopy, dynamic light scattering, and ultraviolet-visible spectrophotometry, respectively. The cell uptake was assayed using the atomic absorption spectrometry. Mitochondrial activity, colony formation, and comet assays were applied to assess and compare the enhanced radiotoxicity of 100 KV and 6 MV X-rays, when combined with Glu-G nanoparticles. RESULTS: Glu-G nanoparticles had no significant toxicity for MCF7 and QU-DB cells up to 100 micromolar concentration. Compared to radiation alone, the intracellular uptake of Glu-G nanoparticles resulted in increased inhibition of cell proliferation by 64.1% and 38.7% for MCF7 cells, and 64.4% and 32.4% for QU-DB cells by 100 kVp and 6 MV X-rays, respectively. Comet assay confirmed an increase of DNA damage as a result of combination of 6 MV photons with Glu-G nanoparticles. CONCLUSION: Glu-G nanoparticles have remarkable potential for enhancing radiotoxicity of both low and high energy photons in MCF7 and QU-DB cells.

The effect of glucose-coated gold nanoparticles on radiation bystander effect induced in MCF-7 and QUDB cell lines.

Due to biocompatibility and relative non-toxic nature, gold nanoparticles (GNPs) have been studied widely to be employed in radiotherapy as radio-sensitizer. On the other hand, they may enhance radiation-induced bystander effect (RIBE), which causes radiation adverse effects in non-irradiated normal cells. The present study was planned to investigate the possibility of augmenting the RIBE consequence of applying glucose-coated gold nanoparticles (Glu-GNPs) to target cells. Glu-GNPs were synthesized and utilized to treat MCF7 and QUDB cells. The treated cells were irradiated with 100 kVp X-rays, and their culture media were transferred to non-irradiated bystander cells. Performing MTT cellular proliferation test and colony formation assay, percentage cell viability and survival fraction of bystander cells were determined, respectively, and were compared to control bystander cells which received culture medium from irradiated cells without Glu-GNPs. Glu-GNPs decreased the cell viability and survival fraction of QUDB bystander cells by as much as 13.2 and 11.5 %, respectively (P < 0.02). However, the same end points were not changed by Glu-GNPs in MCF-7 bystander cells. Different RIBE responses were observed in QUDB and MCF7 loaded with Glu-GNPs. Glu-GNPs increased the RIBE in QUDB cells, while they had no effects on RIBE in MCF7 cells. As opposed to QUDB cells, the RIBE in MCF7 cells did not change in the dose range of 0.5-10 Gy. Therefore, it might be a constant effect and the reason of not being increased by Glu-GNPs.

Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study.

OBJECTIVE: Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. MATERIALS AND METHODS: This experimental study irradiated three groups of target cells for one, two and three times with(60)Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. RESULTS: RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. CONCLUSION: The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy).

In vivo skin dose measurement in breast conformal radiotherapy.

AIM OF THE STUDY: Accurate skin dose assessment is necessary during breast radiotherapy to assure that the skin dose is below the tolerance level and is sufficient to prevent tumour recurrence. The aim of the current study is to measure the skin dose and to evaluate the geometrical/anatomical parameters that affect it. MATERIAL AND METHODS: Forty patients were simulated by TIGRT treatment planning system and treated with two tangential fields of 6 MV photon beam. Wedge filters were used to homogenise dose distribution for 11 patients. Skin dose was measured by thermoluminescent dosimeters (TLD-100) and the effects of beam incident angle, thickness of irradiated region, and beam entry separation on the skin dose were analysed. RESULTS: Average skin dose in treatment course of 50 Gy to the clinical target volume (CTV) was 36.65 Gy. The corresponding dose values for patients who were treated with and without wedge filter were 35.65 and 37.20 Gy, respectively. It was determined that the beam angle affected the average skin dose while the thickness of the irradiated region and the beam entry separation did not affect dose. Since the skin dose measured in this study was lower than the amount required to prevent tumour recurrence, application of bolus material in part of the treatment course is suggested for post-mastectomy advanced breast radiotherapy. It is more important when wedge filters are applied to homogenize dose distribution.