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

The modification of radiation-induced apoptosis in splenocytes by a vitamin -containing dietary supplement was studied, For 45 days prior to irradiatio n at a lethal dose of 6 Gy, mice received a dietary supplement containing v itamins with antioxidant properties and microelements. The expression of TR PM-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-induce d alterations in gene expression were different in the control and the anti oxidant mixture-fed mice. The antioxidant mixture administration resulted i n an inhibition of TRPM-2 expression both before and after irradiation. The bcl-2 mRNA content steadily increased after irradiation in splenocytes fro m antioxidant mixture-fed mice, while in the control group 2-h after irradi ation only trace amount of bcl-2 mRNA was detected. In splenocytes from con trol mice, the expression of superoxide dismutase and catalase genes signif icantly decreased within 2-h after irradiation; whereas in mice receiving t he antioxidant mixture, inhibition of catalase gene expression was not as p rominent. The expression of superoxide dismutase gene was still high 24-h a fter irradiation. The antioxidant administration decreased the radiation-in duced 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. (C) 1999 Elsevier Science I nc.