Modification of p53 protein profile by gamma irradiation followed by methyl donor starvation
- 61 Downloads
The possible beneficial radio-protective effects of one-carbon transfer agents namely folate, choline and methionine have been the subject of extensive investigation. Ionizing radiation is known to extensively damage the DNA. One-carbon transfer agents have been proposed to have important role in context of DNA repair via their role in purine and thymidylate synthesis and in DNA methylation. Sufficient dietary availability of one-carbon transfer agents therefore, might have ability to modify radiation effects. In present study modifications in level of tumor suppressor protein p53 by gamma irradiation followed by methyl donor starvation was observed. Experiments showed an increase in nuclear and cytoplasmic p53 protein concentration in liver, spleen and thymus. The overall rise in the level of p53 protein in liver was found to be less than that in spleen and thymus. Moreover significant heterogeneity in the basal level of expression of the p53 protein in liver, spleen and thymus was observed as the level of p53 protein in spleen and thymus was found to be 7–8 fold more than that in liver. Results indicated that radiation stress followed by methyl donor starvation could significantly induce p53 protein in spleen and thymus where there was a dramatic accumulation of p53 following irradiation, while in other tissues, particularly the liver, no such dramatic response was seen. Folate contribution of intestinal bacteria was found to influence p53 protein levels. Our observations indicated a prominent role played by the methyl donors in protecting the cell against harmful effects of ionizing radiation.
Key wordsγ-radiation methyl donors mice one-carbon transfer p53 protein starvation
Unable to display preview. Download preview PDF.
- 4.Ame BN: DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 475: 7–20, 2001Google Scholar
- 11.Prasad KN,. Cole WC, Hasse GM: Health risks of low dose ionizing radiation in humans: a review. Exp Biol Med (Maywood) 229: 378–382, 2002Google Scholar
- 12.Eliyahu D, Michalovitz D, Eliyahu S, Pinhasikimhi O, Oren M: p53 - Oncogene or anti-oncogene. Oncog Cancer Diagno 39: 125–134, 1990Google Scholar
- 13.Milner JA: Conformation hypothesis for the suppressor and promoter functions of p53 in cell growth control and in cancer. Proc R Soc Lond [Biol] 245: 139–145, 1991Google Scholar
- 26.Dutrillaux B: Ionizing radiation induced malignancies in man. Radioprotection 32: C431–C440, 1997Google Scholar
- 39.Batra V, Kesavan V, Mishra KP: Modulation of folate dependent DNA methyltransferase 1 (dnmt1) activity in whole body γ-irradiated mice. Pteridines 15: 155–160, 2004Google Scholar
- 41.Batra V, Kesavan V, Mishra KP: Modulation of DNA methyltransferase1 profile by gamma irradiation followed by methyl donor starvation. Pteridines 2005 (in press) Author: Please update this reference.Google Scholar
- 42.Kesavan V, Pote MS, Batra V, Viswanathan G: Increased folate catabolism following total body γ-irradiation in mice. J Radiat Res 14: 144–149, 2003Google Scholar