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Title: Transient cell function disruption by low dose acute exposure of ionizing radiation
Authors: Saxena, Priyanka
Bhatnagar, Aseem
Nishad, Dhruv Kumar
Tyagi, Ritu
Rana, Poonam
Ali, Shakir
Mittal, Gaurav
Keywords: Thallium-201
Thyroid stunning
Na+-K+ ATPase pump
Issue Date: Dec-2011
Publisher: NISCAIR-CSIR, India
Abstract: Incubation of BMG-1 cells with thallium chloride (<sup>201</sup>Tl) in the range of diagnostic dose did not show a smooth uptake curve and appeared to have an unsuspected deviation in initial phase. In the present study this unexpected phenomenon was explored, using commonly used radionuclides (viz., <sup>201</sup>Tl and <sup>131</sup>I). Comparison was made with technetium-99m pertechnetate (<sup>99m</sup>TcO<sub>4</sub><sup>-</sup>) and technetium-99m labeled methoxyisobutylisonitrile (<sup>99m</sup>Tc-MIBI) that are known to show conventional 2 phase graph representing inflow and outflow segments. Serial <i style="">in vitro</i>, <i style="">ex-vivo</i> and <i style="">in vivo</i> gamma scintigraphy as well as NMR spectroscopy experiments were conducted to corroborate the results. BMG-1 cells demonstrated a four-phase uptake pattern with <sup>201</sup>Tl as compared to a conventional biphasic pattern with <sup>99m</sup>Tc-MIBI. Flow cytometry data however did not reveal any <sup>201</sup>Tl induced cell injury. Further, mice tissue extracts injected with <sup>201</sup>Tl also showed a transient depression in its uptake. Scintigraphy experiments in rabbits administered with diagnostic dose of <sup>201</sup>Tl and <sup>131</sup>I confirmed the <i style="">in vitro</i> and <i style="">ex vivo</i> findings. Further, proton NMR spectroscopy showed decrease in the level of choline at 3 h and 24 h in <sup>201</sup>Tl treated animals as compared to control. Phosphoethanolamine peak firstly decreased at 3 h but reached normal level at 24 h time point. No significant change was observed in the level of betaine. This transient reduction in internalization of <sup>201</sup>Tl and <sup>131</sup>I may represent a hitherto unknown acute effect of low dose radiation, i.e., transient depression in Na<sup>+</sup>-K<sup>+</sup> ATPase pump activity without any apparent evidence of cell damage, representing a transient cell membrane dysfunction. The phenomenon may present a mechanistical explanation of ‘thyroid stunning’ at cellular level and suggest that it may be more universal in nature than suspected till now.
Description: 895-903
ISSN: 0975-1009 (Online); 0019-5189 (Print)
Appears in Collections:IJEB Vol.49(12) [December 2011]

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