Radiation-induced apoptosis in thymocytes: inhibition by diethyldithiocarbamate and zinc.
Apoptosis is a process of physiological cell death characterized by DNA fragmentation, chromatin condensation, loss of membrane asymmetry, mitochondrial alterations and cell lethality. In the present study, apoptosis induced in thymocytes by gamma irradiation is evaluated by flow cytometry, by a diphenylamine colorimetric method and by gel electrophoresis. Treatment of thymocytes with diethyldithiocarbamate or zinc shows that these compounds can inhibit radiation-induced apoptosis. Moreover, a synergistic effect is observed by using combinations of both compounds: ZnSO4 potentiates the effect of diethyldithiocarbamate at concentrations at which the compounds used separately show a low efficacy. A study of kinetics shows that addition of 1 microM diethyldithiocarbamate + 50 microM ZnSO4 (the most efficient combination) after irradiation can decrease DNA fragmentation even when it is added 2-3 h after irradiation. However, 1 microM diethyldithiocarbamate + 50 microM ZnSO4 cannot prevent the radiation-induced loss of membrane asymmetry and the decrease in alteration of the mitochondrial membrane as measured by binding of merocyanine 540 and uptake of rhodamine 123, respectively.
Mathieu
J
J
Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Ferlat
S
S
Ballester
B
B
Platel
S
S
Herodin
F
F
Chancerelle
Y
Y
Mestries
J C
JC
Kergonou
J F
JF
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053938:DNA Fragmentation; D004050:Ditiocarb / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D013601:T-Lymphocytes / Q000528:radiation effects*; D015032:Zinc / Q000494:pharmacology*
D012235:Rhodamines; D020112:Rhodamine 123; D004050:Ditiocarb; D015032:Zinc; D000111:Acetylcysteine