Effect of antioxidant vitamins on radiation-induced apoptosis in cells of a human lymphoblastic cell line.
Modulating the amount of radiation-induced apoptosis by administering antioxidant vitamins offers a possible way to influence radiation-induced side effects in normal tissues. Therefore, we investigated the effect of beta-carotene, vitamin C and alpha-tocopherol on radiation-induced apoptosis in cells in culture. Human T-lymphoblastic MOLT-3 cells were irradiated with a dose of 3 Gy 1 h after or immediately prior to the addition of vitamins in three concentrations (0.01 microM, 1 microM and 100 microM). Eight hours later, apoptosis was scored morphologically by staining the nuclear DNA with Hoechst 33342. When given prior to irradiation, beta-carotene and vitamin E reduced the amount of radiation-induced apoptosis significantly at concentrations of 0.01 microM and 1 microM. In contrast, vitamin C did not show any protective effect when given at these two concentrations and caused a slight but significant radiosensitization at 100 microM. At 0.01 microM, all combinations of two vitamins showed a protective effect. This was also observed for the combination of all three vitamins at concentrations of 0.01 and 1 microM. When given immediately after irradiation, each of the three vitamins showed a protective effect at 0.01 microM. In addition, the combination of alpha-tocopherol and vitamin C reduced radiation-induced apoptosis slightly when given at 1 microM. In all other cases, no statistically significant modulation of radiation-induced apoptosis was observed. In our experimental system, the protective effect of beta-carotene and vitamin E was dependent on concentration and occurred only in the micromolar and sub-micromolar concentration range, while vitamin C alone, but not in combinations, had a sensitizing effect, thus arguing for a careful consideration of vitamin concentrations in clinical settings.
Ortmann
Elisabeth K
EK
Department of Radiobiology, Clinic for Radiotherapy and Radiobiology General Hospital Vienna, The University of Vienna, Austria.
Mayerhofer
Thomas
T
Getoff
Nikola
N
Kodym
Reinhard
R
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007945:Leukemia, Lymphoid / Q000503:physiopathology; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D014815:Vitamins / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology
D000975:Antioxidants; D014815:Vitamins; D019207:beta Carotene; D024502:alpha-Tocopherol; D001205:Ascorbic Acid