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 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.
Ushakova
T
T
Institute of Theoretical and Experimental Biophysics, Pushchino, Russia.
Melkonyan
H
H
Nikonova
L
L
Afanasyev
V
V
Gaziev
A I
AI
Mudrik
N
N
Bradbury
R
R
Gogvadze
V
V
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001205:Ascorbic Acid / Q000494:pharmacology; D015415:Biomarkers; D002374:Catalase / Q000235:genetics; D002588:Cesium Radioisotopes; D051152:Clusterin; D004032:Diet; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D019254:Genes, bcl-2; D006023:Glycoproteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012431:Rutin / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D013482:Superoxide Dismutase / Q000235:genetics; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology; D014916:Whole-Body Irradiation; D019207:beta Carotene / Q000494:pharmacology
D000975:Antioxidants; D015415:Biomarkers; D002588:Cesium Radioisotopes; C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D019253:Proto-Oncogene Proteins c-bcl-2; D019207:beta Carotene; D014810:Vitamin E; D012431:Rutin; D002374:Catalase; D013482:Superoxide Dismutase; D018038:Sodium Selenite; D001205:Ascorbic Acid