Radiation-induced apoptosis and necrosis in Molt-4 cells: a study of dose-effect relationships and their modification.
Cell death induced by various radiation doses in Molt-4 and L5178Y cells was studied. Molt-4 cells have a low threshold for induction of interphase death while L5178Y cells have a high threshold. Interphase death in Molt-4 cells at doses > 100 Gy and in L5178Y cells at doses > 300 Gy showed typical necrosis. In contrast, cell death in Molt-4 cells after 2-30 Gy had features of both apoptosis and necrosis; the appearance of orcein-stained cells in the light microscope was suggestive of apoptosis, showing chromatin margination and apoptotic bodies. The concomitant appearance of non-viable cells as estimated by either orcein staining or eosin dye staining correlated well with this. Early cell swelling and a diffuse smear pattern in DNA gel electrophoresis were however suggestive of necrosis. Detailed electron microscopic observations revealed that events leading to the interphase death of Molt-4 cells after 2-30 Gy involved complicated pathways which included both apoptotic changes in the nucleus and necrotic changes in the cytoplasm. TPA not only had a protective effect on the interphase death of Molt-4 cells, but also converted the mode of cell death from interphase death to mitotic death after low doses of radiation. Cycloheximide and H-7, known to inhibit apoptosis in irradiated thymocytes, had no protective effect on the interphase death of Molt-4 cells, suggesting that the events leading to interphase death in Molt-4 cells might be different from those in thymocytes. BrdUrd-labelling had a sensitizing effect on the radiation response, but no effect on interphase death in Molt-4 cells thus suggesting that DNA damage may not be responsible for interphase death.
Akagi
Y
Y
Department of Radiology, School of Medicine, Hiroshima University, Japan.
Ito
K
K
Sawada
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007945:Leukemia, Lymphoid; D009336:Necrosis; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects*
D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D001973:Bromodeoxyuridine; D013755:Tetradecanoylphorbol Acetate