Modification of gene expression by dietary antioxidants in radiation-induced apoptosis of mice splenocytes

• Published in: Free radical biology & medicine 1999-04, Vol.26 (7), p.887-891
• Main Authors: Ushakova, Tatyana, Melkonyan, Hovsep, Nikonova, Larisa, Afanasyev, Vladimir, Gaziev, Azhub I, Mudrik, Nikolai, Bradbury, Robert, Gogvadze, Vladimir
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - administration & dosage; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Ascorbic Acid - pharmacology; beta Carotene - pharmacology; Biomarkers; Catalase - genetics; Cell death; Cesium Radioisotopes; Clusterin; Diet; Dietary Supplements; Free radicals; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; Genes, bcl-2; Glycoproteins - genetics; Male; Mice; Mice, Inbred C57BL; Molecular Chaperones; Proto-Oncogene Proteins c-bcl-2 - genetics; Radiation; Rutin - pharmacology; Sodium Selenite - pharmacology; Spleen - cytology; Spleen - drug effects; Spleen - radiation effects; Superoxide Dismutase - genetics; Time Factors; Vitamin E - pharmacology; Whole-Body Irradiation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(98)00281-0

The modification of radiation-induced apoptosis in splenocytes by a vitamin-containing dietary supplement was studied. For 45 days prior to irradiation at a lethal dose of 6 Gy, mice received a dietary supplement containing vitamins with antioxidant properties and microelements. The expression of TRPM-2 (a marker for programmed cell death), bcl-2 (the product of which has been shown to prevent apoptosis), superoxide dismutase, and catalase genes was studied at different time intervals after irradiation. Radiation-induced alterations in gene expression were different in the control and the antioxidant mixture-fed mice. The antioxidant mixture administration resulted in an inhibition of TRPM-2 expression both before and after irradiation. The bcl-2 mRNA content steadily increased after irradiation in splenocytes from antioxidant mixture-fed mice, while in the control group 2-h after irradiation only trace amount of bcl-2 mRNA was detected. In splenocytes from control mice, the expression of superoxide dismutase and catalase genes significantly decreased within 2-h after irradiation; whereas in mice receiving the antioxidant mixture, inhibition of catalase gene expression was not as prominent. The expression of superoxide dismutase gene was still high 24-h after irradiation. The antioxidant administration decreased the radiation-induced apoptosis and delayed internucleosomal fragmentation of DNA. Our data suggest that radiation-induced alteration of gene expression is, at least in part, determined by reactive oxygen species.