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Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation.

Azimian H, Bahreyni-Toossi MT, Rezaei AR, Rafatpanah H, Hamzehloei T, Fardid R - J Med Phys (2015 Jan-Mar)

Bottom Line: In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated.Modification of these gene expressions seems to be a principle pathway in the early radioresistance response.In our study, we found that these changes were temporary and faded completely within a week.

View Article: PubMed Central - PubMed

Affiliation: Medical Physics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

ABSTRACT
Lymphocytes have demonstrated complex molecular responses to induced stress by ionizing radiation. Many of these reactions are mediated through modifications in gene expressions, including the genes involved in apoptosis. The primary aim of this study was to assess the effects of low doses of ionizing radiation on the apoptotic genes, expression levels. The secondary goal was to estimate the time-effect on the modified gene expression caused by low doses of ionizing radiation. Mononuclear cells in culture were exposed to various dose values ranged from 20 to 100 mGy by gamma rays from a Cobalt-60 source. Samples were taken for gene expression analysis at hours 4, 24, 48, 72, and 168 following to exposure. Expression level of two apoptotic genes; BAX (pro-apoptotic) and Bcl-2 (anti-apoptotic) were examined by relative quantitative real-time polymerase chain reaction (PCR), at different time intervals. Radio-sensitivity of peripheral blood mononucleated cells (PBMCs) was measured by the Bcl-2/BAX ratio (as a predictive marker for radio-sensitivity). The non-parametric two independent samples Mann-Whitney U-test were performed to compare means of gene expression. The results of this study revealed that low doses of gamma radiation can induce early down-regulation of the BAX gene of freshly isolated human PBMCs; however, these changes were restored to near normal levels after 168 hours. In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated. Four hours following to exposure to low doses of gamma radiation, apoptotic gene expression is modified, this is manifested as adaptive response. Modification of these gene expressions seems to be a principle pathway in the early radioresistance response. In our study, we found that these changes were temporary and faded completely within a week.

No MeSH data available.


Related in: MedlinePlus

Effect of Gamma radiation of 0–100 mGy on BAX and Bcl-2 expression in human peripheral blood lymphocytes. (a) 4 h (b) 24 h (c) 48 h (d) 72 h (e) 168 h post-irradiation. Each point represents mean value for the four blood samples. Gene expression data are given in terms of the base 2 logarithm of the ratio; positive and negative values represent increased and decreased expression level, respectively. *represents statistically significant difference from controls at P<0.05 and Error bars show standard deviation
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Figure 1: Effect of Gamma radiation of 0–100 mGy on BAX and Bcl-2 expression in human peripheral blood lymphocytes. (a) 4 h (b) 24 h (c) 48 h (d) 72 h (e) 168 h post-irradiation. Each point represents mean value for the four blood samples. Gene expression data are given in terms of the base 2 logarithm of the ratio; positive and negative values represent increased and decreased expression level, respectively. *represents statistically significant difference from controls at P<0.05 and Error bars show standard deviation

Mentions: The results indicate that when lymphocytes are exposed to 20, 50, and 100 mGy of gamma radiation; down-regulation is induced for BAX pro-apoptotic gene 4 hours, 24 hours, 48 hours, and 72 hours following irradiation [Figure 1a–d]. Expression of Bcl-2 anti-apoptotic gene was found to be up-regulated at doses as low as 20 mGy after 48 hours, 72 hours, and 168 hours following irradiation [Figure 1c–e]. The results also show that the Bcl-2 expression was induced by 50 mGy at 24 hours [Figure 1b], 72 hours [Figure 1d], and 168 hours [Figure 1e] following irradiation. In addition, up-regulation of Bcl-2 expression was induced by 100 mGy at 4 hours, 24 hours, 48 hours, 72 hours, and 168 hours after irradiation [Figure 1a–e].


Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation.

Azimian H, Bahreyni-Toossi MT, Rezaei AR, Rafatpanah H, Hamzehloei T, Fardid R - J Med Phys (2015 Jan-Mar)

Effect of Gamma radiation of 0–100 mGy on BAX and Bcl-2 expression in human peripheral blood lymphocytes. (a) 4 h (b) 24 h (c) 48 h (d) 72 h (e) 168 h post-irradiation. Each point represents mean value for the four blood samples. Gene expression data are given in terms of the base 2 logarithm of the ratio; positive and negative values represent increased and decreased expression level, respectively. *represents statistically significant difference from controls at P<0.05 and Error bars show standard deviation
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4471643&req=5

Figure 1: Effect of Gamma radiation of 0–100 mGy on BAX and Bcl-2 expression in human peripheral blood lymphocytes. (a) 4 h (b) 24 h (c) 48 h (d) 72 h (e) 168 h post-irradiation. Each point represents mean value for the four blood samples. Gene expression data are given in terms of the base 2 logarithm of the ratio; positive and negative values represent increased and decreased expression level, respectively. *represents statistically significant difference from controls at P<0.05 and Error bars show standard deviation
Mentions: The results indicate that when lymphocytes are exposed to 20, 50, and 100 mGy of gamma radiation; down-regulation is induced for BAX pro-apoptotic gene 4 hours, 24 hours, 48 hours, and 72 hours following irradiation [Figure 1a–d]. Expression of Bcl-2 anti-apoptotic gene was found to be up-regulated at doses as low as 20 mGy after 48 hours, 72 hours, and 168 hours following irradiation [Figure 1c–e]. The results also show that the Bcl-2 expression was induced by 50 mGy at 24 hours [Figure 1b], 72 hours [Figure 1d], and 168 hours [Figure 1e] following irradiation. In addition, up-regulation of Bcl-2 expression was induced by 100 mGy at 4 hours, 24 hours, 48 hours, 72 hours, and 168 hours after irradiation [Figure 1a–e].

Bottom Line: In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated.Modification of these gene expressions seems to be a principle pathway in the early radioresistance response.In our study, we found that these changes were temporary and faded completely within a week.

View Article: PubMed Central - PubMed

Affiliation: Medical Physics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

ABSTRACT
Lymphocytes have demonstrated complex molecular responses to induced stress by ionizing radiation. Many of these reactions are mediated through modifications in gene expressions, including the genes involved in apoptosis. The primary aim of this study was to assess the effects of low doses of ionizing radiation on the apoptotic genes, expression levels. The secondary goal was to estimate the time-effect on the modified gene expression caused by low doses of ionizing radiation. Mononuclear cells in culture were exposed to various dose values ranged from 20 to 100 mGy by gamma rays from a Cobalt-60 source. Samples were taken for gene expression analysis at hours 4, 24, 48, 72, and 168 following to exposure. Expression level of two apoptotic genes; BAX (pro-apoptotic) and Bcl-2 (anti-apoptotic) were examined by relative quantitative real-time polymerase chain reaction (PCR), at different time intervals. Radio-sensitivity of peripheral blood mononucleated cells (PBMCs) was measured by the Bcl-2/BAX ratio (as a predictive marker for radio-sensitivity). The non-parametric two independent samples Mann-Whitney U-test were performed to compare means of gene expression. The results of this study revealed that low doses of gamma radiation can induce early down-regulation of the BAX gene of freshly isolated human PBMCs; however, these changes were restored to near normal levels after 168 hours. In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated. Four hours following to exposure to low doses of gamma radiation, apoptotic gene expression is modified, this is manifested as adaptive response. Modification of these gene expressions seems to be a principle pathway in the early radioresistance response. In our study, we found that these changes were temporary and faded completely within a week.

No MeSH data available.


Related in: MedlinePlus