Abstract

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].

Highlights

  • Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region

  • Since the normal background radiation in the adjoining coastal areas of Kerala range between < 1.0 to 1.5 mGy/y, the areas with radiation exposures below 1.5 mGy/y have been classified as normal level natural radiation areas (NLNRA), while those above 1.5 mGy/y are considered as ­HLNRA7

  • Studies conducted over several years in this area using various endpoints have not shown any adverse health effects in individuals residing in high level natural radiation area (HLNRA) as compared to ­NLNRA7–10, the underlying biological mechanisms remain unclear

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Summary

Introduction

Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. More than 79% of differentially regulated proteins in each dose group showed coefficient of variation (% CV) value ≤ 20%, indicating good stability among the technical replicates (Supplementary Fig. S1b). The analysis revealed that most pathways over-represented in HLNRA samples belonged to the stress response categories, such as DNA damage response, RNA processing, chromatin modifications, cytoskeletal organization, cell signaling and protein modifications.

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