Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

Kumar, Pradeep; Seshadri, M.; Jaikrishan, G.; Das, Birajalaxmi

doi:10.1016/j.mrfmmm.2015.03.011

Cited by 32 publications

(15 citation statements)

References 55 publications

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“…Increase in oxidative stress may lead to damage to DNA as observed by comet and modified comet assay parameters according to the experiment conducted by Tripathi and Jena 24 . The DNA fragmentation assay for the estimation of DNA damage in mammalian cells has several advantages over other cytogenetic bio-assays 43 . Treatment of mice with CYP significantly increased the DNA damage in the bladder cells.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Thymoquinone against Cyclophosphamide-Induced Hemorrhagic Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression

et al. 2016

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Cyclophosphamide (CYP) induced hemorrhagic cystitis is a dose-limiting side effect involving increased oxidative stress, inflammatory cytokines and suppressed activity of nuclear factor related erythroid 2-related factor (Nrf2). Thymoquinone (TQ), an active constituent of Nigella sativa seeds, is reported to increase the expression of Nrf2, exert antioxidant action, and anti-inflammatory effects in the experimental animals. The present study was designed to explore the effects of TQ on CYP-induced hemorrhagic cystitis in Balb/c mice. Cystitis was induced by a single intraperitoneal injection of CYP (200 mg/kg). TQ was administered intraperitoneally at 5, 10 and 20 mg/kg doses twice a day, for three days before and three days after the CYP administration. The efficacy of TQ was determined in terms of the protection against the CYP-induced histological perturbations in the bladder tissue, reduction in the oxidative stress, and inhibition of the DNA fragmentation. Immunohistochemistry was performed to examine the expression of Nrf2. TQ protected against CYP-induced oxidative stress was evident from significant reduction in the lipid peroxidation, restoration of the levels of reduced glutathione, catalase and superoxide dismutase activities. TQ treatment significantly reduced the DNA damage evident as reduced DNA fragmentation. A significant decrease in the cellular infiltration, edema, epithelial denudation and hemorrhage were observed in the histological observations. There was restoration and rise in the Nrf2 expression in the bladder tissues of mice treated with TQ. These results confirm that, TQ ameliorates the CYP-induced hemorrhagic cystitis in mice through reduction in the oxidative stress, inhibition of the DNA damage and through increased expression of Nrf2 in the bladder tissues.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Thymoquinone against Cyclophosphamide-Induced Hemorrhagic Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression

et al. 2016

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“…So far, no significant changes are observed at phenotype level. This population has also been investigated for several biological end points such as chromosome aberrations, micronuclei, telomere length measurement and quantitation of DNA damage [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].None of the above DNA damage end points have shown significant difference between the population from HLNRA and the adjacent normal level natural radiation areas (NLNRA). The spontaneous level of DNA double strand breaks (DSBs) has not shown any increase in DSBs, rather showed marginal reduction in HLNRA individuals belonging to background dose group >5mGy/year [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…The spontaneous level of DNA double strand breaks (DSBs) has not shown any increase in DSBs, rather showed marginal reduction in HLNRA individuals belonging to background dose group >5mGy/year [ 18 ]. Interestingly, DNA damage and repair study in peripheral blood mono-nuclear cells (PBMC) using gamma H2AX marker and comet assay revealed that individuals from HLNRA groups (>5.0mGy/year) have better repair efficiency as compared to NLNRA group [ 21 , 23 ]. Our group has also shown in vivo radio-adaptive response among HLNRA group of individuals after a challenge dose of 1.0 and 2.0Gy of gamma radiation[ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Global transcriptome profile reveals abundance of DNA damage response and repair genes in individuals from high level natural radiation areas of Kerala coast

Jain

Das

2017

PLoS ONE

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The high level natural radiation areas (HLNRA) of Kerala coast in south west India is unique for its wide variation in the background radiation dose (<1.0mGy to 45mGy/year) and vast population size. Several biological studies conducted in this area did not reveal any adverse effects of chronic low dose and low dose rate radiation on human population. In the present study, global transcriptome analysis was carried out in peripheral blood mono-nuclear cells of 36 individuals belonging to different background dose groups [NLNRA, (Group I, ≤1.50 mGy/year) and three groups of HLNRA; Group II, 1.51–5.0 mGy/year), Group III, 5.01-15mGy/year and Group IV, >15.0 mGy/year] to find out differentially expressed genes and their biological significance in response to chronic low dose radiation exposure. Our results revealed a dose dependent increase in the number of differentially expressed genes with respect to different background dose levels. Gene ontology analysis revealed majority of these differentially expressed genes are involved in DNA damage response (DDR) signaling, DNA repair, cell cycle arrest, apoptosis, histone/chromatin modification and immune response. In the present study, 64 background dose responsive genes have been identified as possible chronic low dose radiation signatures. Validation of 30 differentially expressed genes was carried out using fluorescent based universal probe library. Abundance of DDR and DNA repair genes along with pathways such as MAPK, p53 and JNK in higher background dose groups (> 5.0mGy/year) indicated a possible threshold dose for DDR signaling and are plausible reason of observing in vivo radio-adaptive response and non-carcinogenesis in HLNRA population. To our knowledge, this is the first study on molecular effect of chronic low dose radiation exposure on human population from high background radiation areas at transcriptome level using high throughput approach. These findings have tremendous implications in understanding low dose radiation biology especially, the effect of low dose radiation exposure in humans.

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“…Comet assay was performed using plant extract concentration at IC 50 for each extract according to the method described by Kumar, Seshadri, Jaikrishan, and Das () with slight modification. Briefly, after incubation with the extracts and the controls, cell pellets were obtained via centrifugation and resuspended in PBS.…”

Section: Methodsmentioning

confidence: 99%

Screening of phytochemicals and toxicity of medicinal plants,Dilleniaspecies, reveals potential natural product resources

Thooptianrat

Chaveerach

Sudmoon

et al. 2017

Journal of Food Biochemistry

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Plants in genus Dillenia have traditionally been consumed as foods and used for cancer and diarrhea treatments. Crude hexane extracts of nine species, D. aurea, D. excelsa, D. grandifolia, D. ovata, D. parviflora, D. philippinensis, D. pulchella, D. reticulata, and D. suffruticosa were analyzed for chemical contents via gas chromatography‐mass spectrometry, and for their cytotoxicity and genotoxicity on leukocytes via cell counting and comet assays. Oleamide, a chemopreventive agent which acts against Alzheimer's disease, enhances memory function and promotes sleep, was found at the highest amount (18.05–75.60%). The other components discovered in high amounts were squalene and vitamin E. The IC50 of all studied species was higher than 430 µg/mL. Comet assay indicated insignificant DNA damage (p > .05). These results indicate that the plants containing a high amount of useful phytochemicals are nontoxic to normal human cells, thus may be safely applied for the treatment of Alzheimer's disease and other related conditions. Practical applications Oleamide has an important role in living things, especially in humans. Its functions are, improved memory recovery, induced deep sleep and appetite in elders. Based on the principles of phytotherapy, a plant species actually contains several pharmacological compounds in a different quantity; a medicinal reading should be in a single unit. In agreement with a high quantity of oleamide in Dillenia species, many species would be selected to produce natural products in convenient forms, and in drug discovery, because this serves as active principles in drugs as well as templates for synthesis of new drugs. In this research, seven out of nine species including Dillenia aurea, D. excelsa, D. grandifolia, D. ovata, D. parviflora, D. philippinensis, and D. reticulata contained high amounts of oleamide, were expected to release single medicinal activity, and show no cytotoxicity and genotoxicity. Accordingly, they should effectively be made available in modified forms in order to be health products.

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Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

Cited by 32 publications

References 55 publications

Protective Effect of Thymoquinone against Cyclophosphamide-Induced Hemorrhagic Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression

Protective Effect of Thymoquinone against Cyclophosphamide-Induced Hemorrhagic Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression

Global transcriptome profile reveals abundance of DNA damage response and repair genes in individuals from high level natural radiation areas of Kerala coast

Screening of phytochemicals and toxicity of medicinal plants,Dilleniaspecies, reveals potential natural product resources

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