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  Most popular articles (Since February 29, 2016)

 
 
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REVIEW ARTICLES
Ultraviolet radiation-induced carcinogenesis: Mechanisms and experimental models
Karthikeyan Ramasamy, Mohana Shanmugam, Agilan Balupillai, Kanimozhi Govindhasamy, Srithar Gunaseelan, Ganesan Muthusamy, Beualah Mary Robert, Rajendra Prasad Nagarajan
January-March 2017, 8(1):4-19
DOI:10.4103/0973-0168.199301  
Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis.
  8,433 1,045 21
ABSTRACTS OF ICRR-HHE 2016
International conference on radiation research: Impact on human health and environment (ICRR-HHE 2016) and first biennial meeting of society for radiation research 'Feb. 11-13, 2016'

February 2016, 7(5):2-56
  8,300 1,107 -
REVIEW ARTICLE
Imaging of sella: Pituitary adenoma and beyond
Shilpa Sankhe, Lohith Ambadipudi, Rutwik Ketkar, SK Susheel Kumar
January-March 2020, 11(1):3-16
DOI:10.4103/jrcr.jrcr_23_19  
Sella is a small structure in the skull base housing the pituitary gland. Our aim is to show common and not so common lesions in the sellar-suprasellar region and to highlight unique imaging features which can clinch the diagnosis. A study of pituitary should always include the pituitary–hypothalamic axis. Pituitary masses can be divided into various categories, and the focus of this article will be mainly on primary pituitary tumors. Pituitary adenoma is the most common tumor. Based on the size, it is divided into microadenoma (<1 cm) and macroadenoma (≥1 cm). While radiography and computed tomography were used initially for suspected pituitary tumors, magnetic resonance imaging with its multiplanar imaging and an excellent soft-tissue contrast is the investigation of choice. Dynamic imaging is helpful in diagnosing and localizing microadenomas enabling effective surgical management when medical treatment fails. The sellar region is one of the most anatomically complex central nervous system locations. The key to diagnosis lies in understanding the gross and imaging anatomy by dedicated protocols. Structured reporting of pituitary masses ensures a comprehensive analysis of the lesion, based on several imaging characteristics as described in this article, which is finally aimed at dispensing the information required by the treating physician or surgeon. Imaging can now help in predicting surgical outcome, response to medical treatment, and to avoid complications.
  7,723 900 -
REVIEW ARTICLES
DNA double-strand break repair in mammals
Monica Pandey, Sathees C Raghavan
April-June 2017, 8(2):93-97
DOI:10.4103/jrcr.jrcr_18_17  
Failure in repair of DNA double-strand breaks (DSBs) could result in various disorders in mammals including cancer. Among various exogenous agents, radiation is one of the primary causes for induction of DSBs. Homologous recombination, nonhomologous end-joining, and a less efficient microhomology-mediated end-joining are responsible for repair of DSBs to ensure the genomic integrity and stability. This review highlights DNA damage response (DDR) induced following various insults to the genome and how the DNA repair mechanisms have evolved to restore genomic integrity. We also briefly discuss the potential therapeutic targets associated with DDR and DSB repair and novel inhibitors developed against such targets and their well-defined mechanism of action, which may increase sensitivity to traditional radio- and chemo-therapeutic modalities.
  7,622 840 10
Magnetic hyperthermia therapy: An emerging modality of cancer treatment in combination with radiotherapy
Neena Girish Shetake, Murali M.S Balla, Amit Kumar, Badri Narain Pandey
January-March 2016, 7(1):13-17
DOI:10.4103/0973-0168.184606  
Magnetic hyperthermia therapy (MHT) involves heat generation using magnetic nanoparticles (MNPs) in response to an externally applied alternating current magnetic field. These MNPs can be specifically targeted to the tumor site for homogenous heating. Compared to MHT, conventional methods of HT cause heterogeneous heating of tumor and thus poor efficacy of cancer treatment. MHT has also been shown to effectively eliminate the highly chemo- and radio-resistant cancer stem cells in the tumor mass. Due to their diagnostic capability as well as heat-induced cancer cell killing ability, extensive research has been carried out to develop MNPs as potential cancer theranostic agent. The major focus of MNP research has been to design MNPs formulations for efficient targeting, increased colloidal stability, effective heat generation, and minimal inherent toxicity. A few recent MNPs formulations meet some of the required features and showed promising results in preclinical and clinical studies. HT applied through conventional modes has been combined with chemo- and radiotherapy, owing to its ability to increase oxygenation and drug supply due to vasodilation but has shown a limited success in clinic. However, a great hope has arisen from the MNPs to make combinatorial therapies more successful, not only because of the many advantages of MNPs mentioned but also due to their potential for targeted delivery of a range of anti-cancer drugs and radiosensitizing agents.
  7,058 884 24
Phytochemicals as modulators of ultraviolet-b radiation induced cellular and molecular events: A review
Thangaiyan Radhiga, Balupillai Agilan, Umar Muzaffer, Ramasamy Karthikeyan, Govindasamy Kanimozhi, VI Paul, Nagarajan Rajendra Prasad
January-March 2016, 7(1):2-12
DOI:10.4103/0973-0168.184607  
Ultraviolet (UV) radiation is a very prominent environmental toxic agent. Particularly, UVB (280–320 nm – short wave) wavelength penetrates the epidermis and is completely absorbed in the upper dermis, whereas UVA (320–400 nm - long wave) penetrates to the deeper dermis. UVA is a relatively weak carcinogen than UVB because of its weak strength as a tumor initiating agent. UVB exposure elicits adverse effect which includes sunburn, basal and squamous cell carcinoma, melanoma, cataracts, photoaging of the skin and immunosuppression. Increased ozone depletion and modern lifestyle has increased the amount of UV exposure, and this consequently led to a surge in the incidence of skin cancer. UVB-irradiation acts as both tumor initiator and tumor promoter in animal models. UVB-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. Variety of cellular changes, which includes activation of transcription factors and protein kinases were altered during acute and chronic UVB-exposure. All these events leads to skin cancer development involving DNA damage, inflammation, immunosuppression, epidermal hyperplasia, cell cycle dysregulation, depletion of antioxidant–defenses, and reactive oxygen species generation. An epidemiological study shows that human beings consuming varieties of vegetables and fruits are protected from UVB induced carcinogenesis. In the recent years, number of experimental evidences showed that natural nutraceuticals and phytoceuticals are vital targets for UVB-mediated cellular and molecular events and prevents cellular milieu from UVB mediated health effects. In this review, we have discussed the current progress in the study on UVB-mediated signaling that can be exploited as targets for phytochemicals.
  6,665 791 13
ORIGINAL ARTICLES
Radiographic assessment of protective aprons and dose simulation to personnel
Akintayo Daniel Omojola, Michael Onoriode Akpochafor, Samuel Olaolu Adeneye, Ukeme Pius Aniekop
April-June 2019, 10(2):117-123
DOI:10.4103/jrcr.jrcr_14_19  
Background: Studies have shown that protective aprons are carelessly handled after working hours. This, in turn, leads to crack, tear, hole, and creases on the apron, which may lead to distortion in the attenuating property and hence reduction in efficiency. Aim and Objective: The aim of the study was to carry out the radiographic assessment of four protective aprons (denoted A–D), to check for tear, crack, or pressure marks and to simulate what the equivalent dose rate, dose/procedure, percentage absorbance, and transmission factor (TF) would be if a physician is to perform hysterosalpingogram (HSG), for which he/she will be averagely exposed twice/procedure. Materials and Methods: This study used a functional mobile X-ray unit, four protective aprons, a measuring tape, an electronic dosimeter and a locally designed phantom as materials. The first phase involved the radiographic exposure of the protective aprons. The second phase involved the use of a plastic phantom to produce scatter, a wooden T-stand to hold the apron, which was positioned 1.6 m diagonally from the X-ray collimator. This position was assumed to be where a physician would stand during the procedure. Results: Two out of the four aprons were defective (50%). One out of the four aprons was rejected because it exceeded the 670 mm[2] criteria for acceptance. The mean estimated dose/procedure was 65.69–347.56 μSv, and the estimated mean dose per year for 0.25, 0.35, and 0.50 mm protective aprons was 35,592, 9689, and 7900 μSv/year, respectively. TF for 0.25, 0.35, and 0.50 mm protective aprons was 20.4–23.2, 5.3–6.9, and 3.7%–6.3%, respectively. Absorbance for 0.35 and 0.50 mm protective aprons was ≥94%. There was no statistically significant difference in mean percentage absorbance for 0.25 mm protective aprons, compared to other studies (P = 0.981). Conclusion: Estimated equivalent skin dose per year to a physician with 0.25, 0.35, and 0.50 mm protective aprons was below 500 mSv/year, and the mean percentage absorbance for 0.25 mm protective aprons was seen to be below 90%.
  6,598 515 -
REVIEW ARTICLES
Understanding the basic role of glycocalyx during cancer
Yogendrakumar Harivansh Lahir
July-September 2016, 7(3):79-84
DOI:10.4103/0973-0168.197974  
Metastasis or cancer is a functional, molecular and structural disorder which has been an unsolved and fatal mystery and leads to death in most of the individuals suffering from it in spite of the advances made in biomedical and oncological fields. Structurally a tissue consists of cells enclosed by glycocalyx (partially or completely), extracellular matrix incorporating lymphatic and mircovessels. There is a specific amount of glycocalyx sandwiched between extracellular cell matrix and cell membrane depending on the type of the tissue and cell and their location in the biosystems. The common constituents of glycocalyx include biomolecules such as glycolipids, glycoproteins, and oligosaccharides; the glycoproteins are trans-membrane proteins. Any impact due to the interaction between inter- and/or intra-cellular biomolecules or any expected xenobiotics affect extracellular matrix, glycocalyx, cell membrane, cell organelles; these are the prime targets for the investigation related to metastasis. Somehow or the other the glycocalyx has attracted relative less attention of the researchers. The various aspects of the prometastatic interactions involve ligand-receptors, integrins, and other cellular receptors; glycocalyx has its role in such interactions. There are changes in the physicochemical parameters of glycocalyx which affect the cell membrane adversely. These result in malfunctioning of cell signaling, cell proliferation, cell migration, etc. There have been relatively less reports on the structural and functional changes in glycocalyx specifically related to circulating tumor cells and the cancerous cells of organs such as ovary, breast tissue, lungs, and hepatic tissues. In this presentation, an effort is made to review and evaluate the changes in glycocalyx during such interactions between the glycocalyx and the prometastatic molecules.
  6,328 516 6
Current status of radiation countermeasures for acute radiation syndrome under advanced development
Vijay K Singh, Oluseyi O Fatanmi, Paola T Santiago, Madison Simas, Briana K Hanlon, Melissa Garcia, Stephen Y Wise
January-March 2018, 9(1):13-27
DOI:10.4103/jrcr.jrcr_3_18  
The availability of safe and effective radiation countermeasures for the military and civilian population represents a significant unmet medical need. To expedite the development of countermeasures for life-threating situations, the United States Food and Drug Administration (US FDA) has implemented the “Animal Rule” which applies to the development and evaluation of drugs and biologics to reduce or prevent life-threatening conditions caused by exposure to lethal or permanently disabling agents where human efficacy trials are neither feasible nor ethical. In addition, the FDA has introduced several incentives (fast track, orphan drug status, and emergency use authorization [EUA]) to attract drug sponsors to develop such agents for human use. Repurposing is vital to make drugs available for life-threatening conditions. Drugs are commonly repurposed for new indications not originally envisioned. By repurposing a drug, it can be made available for human use much quicker, but this pathway also involves issues such as intellectual property rights as corporations are reluctant to expose their blockbuster pharmaceuticals to additional scientific scrutiny. Two radiomitigators for hematopoietic acute radiation syndrome (H-ARS) (Neupogen and Neulasta) have been approved by the FDA through repurposing. The EUA is a legal means for the FDA to approve new drugs or new indications for the previously approved drugs for use during a declared emergency and is a valid way to expedite drug development. Several promising agents with and without FDA investigational new drug (IND) status for ARS are under advanced development. In the next few years, we expect that the FDA will approve a few radioprotectors for H-ARS as well as gastrointestinal ARS via Animal Rule.
  6,126 713 9
ORIGINAL ARTICLE
Mass attenuation coefficient and its photon interaction derivables of some skeletal muscle relaxants
HC Manjunatha
January-March 2016, 7(1):18-26
DOI:10.4103/0973-0168.184608  
Context: The study of photon interactions with biological materials is essential in radiation medicine and biology, nuclear technology and space research, since radioactive sources are used. Aims: A study of mass attenuation coefficient, effective atomic numbers (Zeff) and electron density of some commonly used skeletal muscle relaxants. Materials and Methods: We have measured the mass attenuation some commonly used skeletal muscle relaxants such as tubocurarine chloride, gallamine triethiodide, pancuronium bromide, suxamethonium bromide and mephenesin for various gamma sources of energy ranging from 84keV to 1330 keV (170Tm, 57Co, 141Ce, 203Hg, 51Cr, 113Sn, 22Na, 137Cs, 60Co, 22Na and 60Co). The measured values agree with the theoretical values. The effective atomic numbers (Zeff) and electron density (Ne) of commonly used skeletal muscle relaxants for total and coherent, incoherent, photoelectric absorption, pair production in atomic and nuclear field photon interaction have been computed in the wide region 1keV to 100GeV using an accurate database of photon-interaction cross sections and the WinXCom program. Results: The significant variation of Zeff and Nel is due to the variations in the dominance of different interaction process in different energy regions. A comparison is also made with the single values of the Zeff and Nel provided by the program XMuDat. We have also calculated CT numbers, kerma values relative to air and dose rate for relaxants which are also not remaining constant with energy. Conclusions: The computed data of mass attenuation coefficient, effective atomic numbers (Zeff) and electron density and CT numbers in the low energy region helps in visualizing the image of the biological samples and precise accuracy in treating the inhomogenity of them in medical radiology. The calculated kerma values relative to air and dose rate for relaxants are useful in radiation medicine.
  5,942 490 4
REVIEW ARTICLES
Ellagic acid radiosensitizes tumor cells by evoking apoptotic pathway
Vidhula R Ahire, KP Mishra
July-September 2016, 7(3):71-78
DOI:10.4103/0973-0168.197973  
Cancer causes millions of deaths each year globally. In most patients, the cause of treatment failure is found associated with the resistance to chemotherapy and radiotherapy. The development of tumor cell resistance evokes multiple intracellular molecular pathways. In addition, the limitation in treatment outcome arises due to unintended cytotoxic effects of the synthetic anticancer drugs to normal cells and tissues. Considerable focus of research is, therefore, devoted to examine plant-based herbal compounds which may prove potential anticancer drug for developing effective cancer therapy. Research results from our laboratory have shown that ellagic acid (EA), a natural flavonoid displays enhanced tumor toxicity in combination with gamma radiation to many types of cancers in vitro as well as in vivo. Studies on the underlying mechanisms of toxicity suggest that EA employs the cellular signaling pathways in producing the observed effects. This paper gives an account of molecular mechanisms of EA-induced apoptosis process in tumor cytotoxicity. It is suggested that EA acts as a novel radiosensitizer for tumors and a radioprotector for normal cells which may offer a novel protocol for cancer treatment.
  5,647 524 4
Radiation oxidative stress in cancer induction and prevention
Prabodha Kumar Meher, Kaushala Prasad Mishra
January-March 2017, 8(1):44-52
DOI:10.4103/jrcr.jrcr_10_17  
Exposure of cells to ionizing radiation causes generation of intracellular reactive oxygen species (ROS) which are implicated in the mechanism of carcinogenesis. Molecular steps involved in the transformation of normal cells to cancer cells have been enigmatic but generally believed to arise from aberration in cellular redox homeostasis. In normal cell function, a delicate balance is maintained between ROS generated in the metabolic process and level of endogenous antioxidant defense. ROS are known to regulate various cellular functions, such as cell division, signal transduction, and apoptosis. Cells experience oxidative stress when excess production of ROS occurs inside a cell upon exposure to external stressor agents. This redox imbalance affects the cellular functions due to DNA strand breaks, chromosomal aberrations, gene mutations, alteration in signal transduction, and inhibition of apoptosis leading to induction of cancer and other diseases. Radiation-induced ROS are involved in initiation and promotion of carcinogenesis. Therefore, detoxification of ROS by exogenous antioxidants including dietary polyphenols offers an important strategy for cancer prevention. Recent research results have shown that resistance of cancer stem cells to therapies is linked to low level of ROS. Interestingly, in vitro and in vivo experiments have reported that radiotherapy- and chemotherapy-induced ROS in cytosol sensitize the tumor cells to death, resulting in tumor growth retardation. This review is an attempt to delineate mechanisms of ROS in carcinogenesis and prevention by dietary compounds. Natural polyphenols and dietary antioxidants hold potential to prevent cancer. Interventions in ROS-mediated signal alteration, apoptosis activation, and modulation of epigenetic processes may offer effective cancer prevention strategy.
  5,380 564 4
Acute radiation syndrome: An update on biomarkers for radiation injury
Vijay K Singh, Paola T Santiago, Madison Simas, Melissa Garcia, Oluseyi O Fatanmi, Stephen Y Wise, Thomas M Seed
October-December 2018, 9(4):132-146
DOI:10.4103/jrcr.jrcr_26_18  
The possible detonation of a radiological dispersal device or improvised nuclear device in a metropolitan city, or the accidental exposures to a radiation source, nuclear accidents, or the all-to-often threats of radiological/nuclear terrorism have led to the urgent need to develop essential analytic tools to assess such radiation exposures, especially radiation doses to exposed individuals. This exposure-assessing work using biological samples, and discipline, is known as biodosimetry. As of late, this field has progressed significantly as it has made use of the advances within newer areas of biologic analytics, namely omics (genomics, proteomics, metabolomics, and transcriptomics), lymphocyte kinetics, optically stimulated luminescence, and electron paramagnetic resonance technology in addition to conventional cytogenetic techniques. The use of automated high throughput platforms and the planning for laboratory surge capacity during the time of need are the latest developments in the field of biomarkers for biodosimetry. Such biomarkers are also needed for radiation exposure/dose conversion estimates that are essential for the development and application of radiation countermeasures, from animals to humans and that are currently being developed following the US Food and Drug Administration Animal Rule. Here, we present and discuss the current status of various biomarkers for assessing radiation dose after radiation exposure. It is anticipated that with the advent of improved biomarkers and associated biomarker platforms for the acute radiation syndrome, exposed victims can be more efficiently triaged and appropriately treated than is currently allowable. The latest advances in the field, and identify the areas where improvement is needed are also listed and discussed.
  5,352 552 6
REVIEW ARTICLE
Mobile phone use and cancer: Does dose really matter?
SMJ Mortazavi, Kaushala P Mishra
October-December 2017, 8(4):165-167
DOI:10.4103/jrcr.jrcr_39_17  
The past decades have witnessed rapid evolution of telecommunication technology and wireless devices. Due to these rapid advances, cell phone usage has remarkably increased the level of human exposure to radiofrequency-electromagnetic fields (RF-EMFs). In the past, it was widely believed that, RF-EMF, in contrast to ionizing radiation, does not have enough energy for ionizing atoms and hence does not cause DNA damage which can lead to cancer. However, substantial evidence now indicates that RF-EMFs increase the reactive oxygen species production and DNA damages which play an important role in the initiation and progression of cancer. Currently, there is no widely accepted answer to this question whether there is a relationship between exposure to RF-EMFs from cell phones and cancer incidence and mortality. Although it seems that this issue is a long-term unsolved problem, new studies have raised new concerns over the safety of mobile phones. Mortazavi have previously studied the health effects of cellular phones, mobile base stations, and Wi-Fi. They have also reviewed reports claiming no link between exposure to RF and brain cancer. They found that in many cases there were large errors and/or major shortcomings in these articles. They have also reported that current controversies may be caused by the key parameter of the large difference in the magnitude of exposures to RF-EMFs in different studies. In this light, in a similar pattern with ionizing radiation, a nonlinear J-shaped dose–response relationship for the carcinogenesis of nonionizing RF-EMF is introduced.
  4,916 639 -
TECHNICAL REPORT
Modified comet assays for the detection of cyclobutane pyrimidine dimers and oxidative base damages
Ganesan Muthusamy, Agilan Balupillai, Kanimozhi Govindasamy, Karthikeyan Ramasamy, Veeramani Kandan Ponniresan, Illiyas Magbool Malla, Rajendra Prasad Nagarajan
January-March 2017, 8(1):82-86
DOI:10.4103/0973-0168.199312  
The comet assay (also known as single-cell gel electrophoresis) is a technique for the detection of DNA damage at the level of the individual cell. It is a versatile, relatively simple to perform and sensitive method. Although most investigations make use of its ability to measure DNA single-strand breaks, modifications to the method allow detection of cyclobutane pyrimidine dimers (CPDs), crosslinks, base damage, and apoptotic nuclei. Many investigators also interested in examining the DNA damage as a function of time after exposure to a known genotoxic agent. Here, we present a procedure of comet assay for the detection of DNA strand breaks, base damages, and CPDs that can be used to measure DNA damage during toxicity, oxidative stress, and ultraviolet radiation exposure and it can be applied in human toxicological biomonitoring scenarios.
  4,937 501 11
ORIGINAL ARTICLES
Thyroid nodule prevalence among young residents in the evacuation area after fukushima daiichi nuclear accident: Results of preliminary analysis using the official data
Suminori Akiba, Athira Nandakumar, Kenta Higuchi, Mayumi Tsuji, Futoshi Uwatoko
October-December 2017, 8(4):174-179
DOI:10.4103/jrcr.jrcr_42_17  
Introduction: The nuclear accidents at Fukushima Daiichi Nuclear Power Plant released more than 10 EBq (exabecquerel) of the radionuclides into the atmosphere. A primary health concern after the nuclear accident is the internal exposure of children to radioactive iodines, which are known to accumulate in the thyroid, and to cause neoplasm. Fortunately, studies conducted so far have shown that the thyroid doses from internal exposure to 131I were low, and therefore, any excess risk of thyroid cancer among residents is considered unlikely to be detected in the future. Data and Analysis: Approximately half a year after the accident, the Fukushima Health Management Survey was started. It includes the thyroid screening survey using ultrasonography and a program to estimate the individual radiation dose of residents and evacuees. Results and Discussions: The first-round thyroid survey, which was conducted during the period 2011–2013, covered 300,476 young residents, approximately 82% of residents eligible for the survey, and found thyroid nodules in 3990 examinees. The prevalence of nodules in the evacuation zone was similar to that in the nonevacuation zone. The second-round survey, which was conducted during the period 3–6 years after the accident, detected 3788 participants with thyroid nodules among 270,511 examinees (approximately 71% of eligible residents). The prevalence of thyroid nodules in the evacuation zone was significantly higher than that in the rest of area (relative risk = 1.32; 95% confidence interval = 1.19, 1.45). Conclusion: Further studies are necessary to evaluate the scientific significance of present findings.
  4,897 378 3
Water-soluble version of SCR7-pyrazine inhibits DNA repair and abrogates tumor cell proliferation
Monica Pandey, Vidya Gopalakrishnan, Hassan A Swarup, Sujeet Kumar, Radha Gudapureddy, Anjana Elizabeth Jose, Supriya V Vartak, Robin Sebastian, Mrinal Srivastava, Bibha Choudhary, Mantelingu Kempegowda, Subhas S Karki, Sathees C Raghavan
January-March 2019, 10(1):27-43
DOI:10.4103/jrcr.jrcr_24_18  
Aim: Mammalian DNA Ligases play pivotal role in processes such as DNA replication, recombination, and repair, which qualifies them as potent therapeutic targets to eradicate cancer cells. Recently, we have identified a small molecule inhibitor, SCR7 and its oxidized form SCR7-pyrazine (2-mercapto-6,7-diphenylpteridin-4-ol) (SCR7-P), which can inhibit nonhomologous end-joining (NHEJ) in a Ligase IV-dependent manner. In the present study, we describe a water-soluble version of ligase inhibitor, sodium salt of SCR7-P (Na-SCR7-P) and its anti-tumor effects. Materials and Methods: Water soluble version of SCR7-P was synthesised. To study the inhibitory effect of Na-SCR7-P on ligases, we did in vitro DNA end joining assays using double strand DNA substrates. For this, different concentrations of Na-SCR7-P was used along with purified ligases or cell-free extracts. Further, cytotoxicity induced by Na-SCR7-P was evaluated through trypan blue exclusion assay, JC-1 assay and cell cycle analysis. Anti-tumor activity of Na-SCR7-P was investigated in Swiss albino mice and its off-target effects were studied by conducting kidney and liver test and histological evaluation. Further, the anti-angiogenic effect of the compound was studied using in ovo chorioallantoic membrane assay. Results: Na-SCR7-P inhibited NHEJ in a Ligase IV-dependent manner. However, unlike SCR7 and SCR7-P, it blocked joining catalyzed by all three ligases in vitro, making it an ideal cancer therapeutic agent, as it may target multiple DNA transaction processes within the cancer cells. Na-SCR7-P decreased mitochondrial membrane potential (MMP) leading to cell death in cancer cells. Importantly, the administration of Na-SCR7-P led to a significant reduction in tumor growth from 12th day of treatment, and its impact was significantly higher than previously described SCR7, which targets Ligase IV within cells. Antitumor activity of Na-SCR7-P in mice resulted in enhanced lifespan, with minimal side effects. In addition, the in ovo chorioallantoic membrane assay revealed potent antiangiogenic property of Na-SCR7-P. Conclusion: Our results suggest that Na-SCR7-P can target NHEJ and other DNA repair pathways by disrupting Ligase mediated joining and can potentially be used as a strategy for cancer treatment, owing to its water solubility.
  4,642 409 10
REVIEW ARTICLES
Mechanism of carcinogenesis after exposure of actinide radionuclides: Emerging concepts and missing links
Rakhee Yadav, Manjoor Ali, Amit Kumar, Badri N Pandey
January-March 2017, 8(1):20-34
DOI:10.4103/0973-0168.199304  
Radiation carcinogenesis may be associated with external and/or internal sources of radiation exposure during accidental, occupational, or diagnostic/therapeutic conditions. Most of the radiation carcinogenic events are established after acute doses of low linear energy transfer external radiation. Moreover, the carcinogenic effects of internalized radioisotopes are also reported at their acute/chronic doses. In this regard, actinide radionuclides (like 238U, 239Pu, 232Th, and 241Am) are of great importance as fuel material or waste generated during nuclear power production. These radionuclides may result in incidence of cancer when internalized at high doses while accidental or occupation exposure. Even though the basic carcinogenic mechanism after external or internal radiation exposure remains the same, the magnitude of systemic or target specific radiation effects may vary in these radiation exposure conditions. The majority of the studies investigating biological, carcinogenic, and other health effects of actinide radionuclides are limited only up to quantification of these effects without much mechanistic insights. Moreover, the radiobiological processes, such as bystander effect, genomic instability, and adaptive response, governing the cellular radiosensitivity of targeted/nontargeted cells also need to be studied in the context of carcinogenesis after actinide radionuclides internalization. The review aims to highlight the emerging radiobiological concepts and missing links about actinide radionuclides-induced carcinogenesis. In addition, an overview has been presented about biological and health effects of major actinide radionuclides.
  4,582 446 4
TECHNICAL REPORT
Technical note on cytokinesis-arrested binucleated cell and micronucleus assay
Karthik Kanagaraj, Venkateswarlu Raavi, Shangamithra Visweswaran, Tamizh Gnanasekaran Selvan, Shanmugapriya Dhanashekaran, Venkatachalam Perumal
October-December 2017, 8(4):180-185
DOI:10.4103/jrcr.jrcr_40_17  
Conventionally, many biomarkers are being in use as a measure to genotoxicity in occupational exposure to chemicals, pesticides, radiation, and drug screening. Of which, the micronucleus assay is a preferred choice for many of those applications owing to its simplicity and rapidity. The assay methodology has evolved in cell preparations, staining, and scoring methods: from quantifying the DNA damage in mononucleated cells and binucleated cells; solid (Giemsa) and fluorescence staining (propidium iodide/DAPI); and manual and automated microscopy scoring and flow cytometry. Despite the advantages, preparation of cells with good morphology to interpret DNA damage from a different type of cells remains a challenge in particular for laboratory being the processes of developing the assay. Therefore, the aim of the present report was to explain the micronuclei (MN) assay and means to overcome the troubleshoot for reliable outcome measure using cytokinesis-arrested micronucleus (CBMN) assay from suspension and adherent cultures.
  4,581 436 1
REVIEW ARTICLE
Thermal and nonthermal effects of radiofrequency on living state and applications as an adjuvant with radiation therapy
Andras Szasz
January-March 2019, 10(1):1-17
DOI:10.4103/jrcr.jrcr_25_18  
One of the most frequently applied bioelectromagnetic effects is the deep heating of living species with electromotive force energy. Despite its long history, hyperthermia is a rarely applied oncotherapy because of controversial results and complicated control. The challenge in clinical studies of oncological hyperthermia is the disharmony of the local response and local control with overall survival. Both whole-body (complete isothermia for the body) and local (isothermia for the chosen target) heating show excellent local effects; however, this is not followed with the expected elongation of survival time. A possible solution could be nonisothermal heating to the heterogeneity of the malignancy itself. The distinguishing parameters to select the target are the electromagnetic properties of the malignant tissue together with the physiological differences between malignant cells and their healthy counterparts. Selection could allow for cellular targeting, generating natural reactions, such as programmed cell death (apoptosis) followed by immunogenic cell death involving extended immune reactions. This complex method is a new kind of hyperthermia, named modulated electrohyperthermia (tradename oncothermia). The selective, nonequilibrium energy absorption is well synergized with modern radiation therapies, presenting a solution of an active and controllable tumor-specific immune reaction and subsequent abscopal effects.
  4,523 461 7
REVIEW ARTICLES
Tobacco-induced carcinogenesis and chemoprevention by some natural products
Debolina Pal, Subhayan Sur, Prosenjit Saha, Chinmay Kumar Panda
January-March 2017, 8(1):35-43
DOI:10.4103/jrcr.jrcr_9_17  
Tobacco habit is one of the main etiological factors responsible for cancer in body's multiple organs due to the presence of numerous carcinogens. In different animal models, it was evident that the carcinogens could induce carcinogenesis in multiple organs depending on its route of exposure site (e.g., skin, oral cavity, and lung), metabolism (e.g., liver and lung), and excretion (e.g., lung and kidney). It was evident that the active carcinogen metabolites could induce cellular reactive oxygen species (ROS) level, bind to DNA/RNA/proteins, thereby transforming the stem cell of the specific organs toward neoplasm. Different epidemiological studies including our own showed few natural compounds might reduce the risk of tobacco-induced carcinogenesis. The anticarcinogenic roles of crude extract as well as active compounds of such natural dietary ingredients were also evaluated by several in vivo animal models. Most of the active components have potential antioxidative, anti-inflammatory, and anticarcinogenic roles. For better understanding, the roles of three different types of compounds were selected for this review 1. Tea polyphenols from Camellia sinensis: epigallocatechin gallate and theaflavin; 2. amarogentin from Swertia chirata; and 3. Eugenol from Syzygium aromaticum. Studies showed that three types of compounds could restrict the carcinogenesis in different organs at premalignant stages. This might be due to antioxidation and activation of detoxification system, inhibition of cancer initiating stem cell population, modulation of multiple cellular pathways associated with cell cycle, cell proliferation, and survival which ultimately lead to restrict tumor development at initiation/promotion stage.
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EDITORIAL
Carcinogenic risk from low-dose radiation exposure is overestimated
Kaushala P Mishra
January-March 2017, 8(1):1-3
DOI:10.4103/jrcr.jrcr_12_17  
  4,390 506 4
REVIEW ARTICLES
Histone variant H3.3 and its future prospects in cancer clinic
Divya Reddy, Sanjay Gupta
January-March 2017, 8(1):77-81
DOI:10.4103/jrcr.jrcr_4_17  
Histone variant, H3.3 has been a continuous subject of interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication-independent, unlike the replication-coupled deposition of its canonical counterparts H3.1/3.2. Second, H3.3 has been consistently associated with an active state of chromatin. Apart from this function research in the past few years has also revealed that H3.3 has a central role to play in maintaining the somatic cell identity, for efficient ultraviolet induce DNA damage repair and proper segregation of chromosomes during cell division. Further, the discovery of “driver mutations” on this variant has bought it to limelight in cancer biology to the extent that “oncohistone,” a new term has been coined for different mutants of H3.3. Here, we review the functional importance of H3.3 in the context of cancer.
  4,400 450 1
MEETING REPORT
Radiation carcinogenesis: Mechanisms and experimental models - A meeting report
Nagarajan Rajendra Prasad
April-June 2017, 8(2):114-117
DOI:10.4103/jrcr.jrcr_22_17  
The first International School on Radiation Research (2017) of Society for Radiation Research on the theme of “Radiation Carcinogenesis: Mechanisms and Experimental Models” was held in the Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India, during February 2–4, 2017. The school gathered basic/translational scientists and young researchers interested in recent developments in molecular and clinical aspects of cancer and radiation carcinogenesis. The objective of the School was to educate and train the young researchers about the theoretical and practical aspects of radiation carcinogenesis. The renowned faculties from India and aboard delivered expert lectures and conducted practical sessions during the school. The topics ranged from the basics of cancer and carcinogenesis; role of DNA damage and genomic instability in the mechanism of carcinogenesis; heavy metal radionuclides induced carcinogenesis; low-dose radiobiology and risk of cancer; ultraviolet (UV)-induced carcinogenesis; experimental models for carcinogenesis studies, and cancer incidence during cancer radiotherapy. During the practical session, demonstrations were arranged of techniques such as DNA damage, apoptosis, measurement of reactive oxygen species, mitochondrial membrane potential, fluorescence in situ hybridization, animal model of UV carcinogenesis, and histopathological observations of various stages of oral cancer. This report presents a brief overview of the scientific and practical sessions of the school.
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EDITORIAL
Transition: Translation and a view of the future of radiation biology
Nagraj G Huilgol
February 2016, 7(5):1-1
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