Radio-adaptive response in peripheral blood lymphocytes of individuals residing in high-level natural radiation areas of Kerala in the southwest coast of India

Ramachandran, E.N.; Karuppasamy, C.V.; Kumar, Vinay; Soren, David; Kumar, Pradeep; Koya, P. K. M.; Jaikrishan, G.; Das, Birajalaxmi

doi:10.1093/mutage/gew057

Cited by 15 publications

(13 citation statements)

References 61 publications

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“…Eventually, candidate proteins will be validated with targeted proteomics to identify persistent dose-dependent signatures and radiation biomarkers for molecular epidemiology. Nonetheless, the large scale proteomic changes observed provide a molecular basis for the lack of genomic instability 69,70 and indication of radio-adaptive response 16,71 reported earlier in HLNRA individuals. A previous study from our group showed that HLNRA PBMCs when challenged with an ex-vivo dose of 2 Gy respond with induced expression of several critical proteins to maintain adaptive homeostasis 16 .…”

Section: Discussionmentioning

confidence: 71%

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Nishad

Chauhan

Sowdhamini

et al. 2021

Sci Rep

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Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from ≤ 1 to ≥ 45 mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans. We performed quantitative discovery proteomics based on multiplexed isobaric tags (iTRAQ) coupled with LC–MS/MS on human peripheral blood mononuclear cells from HLNRA individuals. Several proteins involved in diverse biological processes such as DNA repair, RNA processing, chromatin modifications and cytoskeletal organization showed distinct expression in HLNRA individuals, suggestive of both recovery and adaptation to low dose radiation. In protein–protein interaction (PPI) networks, YWHAZ (14-3-3ζ) emerged as the top-most hub protein that may direct phosphorylation driven pro-survival cellular processes against radiation stress. PPI networks also identified an integral role for the cytoskeletal protein ACTB, signaling protein PRKACA; and the molecular chaperone HSPA8. The data will allow better integration of radiation biology and epidemiology for risk assessment [Data are available via ProteomeXchange with identifier PXD022380].

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Section: Discussionmentioning

confidence: 71%

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Nishad

Chauhan

Sowdhamini

et al. 2021

Sci Rep

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“…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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“…Ramachandran et al [22] observed significantly lower frequency of MN in elder (>40 years) individuals from high-dose group of HBRA as compared to the young (≤40 years) individuals after 1.0 Gy ( P < 0.001) and 2.0 Gy ( P = 0.002) of challenging doses. However, the basal frequency of MN was also comparable across NBRA and HBRA group ( P = 0.64).…”

Section: Resultsmentioning

confidence: 99%

Micronucleus Assay-based Evaluation of Radiosensitivity of Lymphocytes among Inhabitants Living in High Background Radiation Area of Mamuju, West Sulawesi, Indonesia

et al. 2018

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Naturally occurring radiation can be found all around us and account for most of the radiation received by human beings each year. Indonesia has a region with high-dose natural radiation located in the suburb of West Sulawesi province with a dose rate up to 2800 nSv/h; however, its impact was not fully understood. The aim of this study was to evaluate the radiosensitivity of 12 peripheral blood lymphocytes of inhabitant from high background radiation area (HBRA) and 10 from normal background radiation area (NBRA) based on cytokinesis-block micronucleus (CBMN) assay after challenged with 1.5 Gy of gamma ray. The analysis of CBMN was done according to standard procedure as per IAEA guidelines, and frequency of binucleate (mitotic) cells with micronuclei (MN) was scored in around 2000 binucleate lymphocytes cells per culture in microscopic analysis. Mean MN frequency for HBRA was lower than that of NBRA (0.121 vs. 0.189) after irradiation, indicating an adaptive response in HBRA group that resulted in less radiosensitivity; however, there was no statistically significant different ( P > 0.05) between these two groups. The MN number was higher in women compared to men for both HBRA (0.15 vs. 0.09) and NBRA (0.216 vs. 0.147) groups. Besides, there was no statistically significant difference ( P > 0.05) in Nuclear Division Index (NDI), as measured in 500 metaphase cells with published formula, between HBRA and NBRA samples (1.24 vs. 1.21). The lower MN frequency prompts us to conclude that there is an adaptive response in the lymphocytes of inhabitants as an indicator of lower radiosensitivity to the high natural radiation exposure. Further studies using large number of samples are required to obtain more comprehensive conclusion along with the assessment of other types of radiosensitivity-related biomarkers.

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Radio-adaptive response in peripheral blood lymphocytes of individuals residing in high-level natural radiation areas of Kerala in the southwest coast of India

Cited by 15 publications

References 61 publications

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

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

Micronucleus Assay-based Evaluation of Radiosensitivity of Lymphocytes among Inhabitants Living in High Background Radiation Area of Mamuju, West Sulawesi, Indonesia

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