Cell cycle regulators modulating con A mitogenesis and apoptosis in low-dose radiation-exposed mice.
Low doses of ionizing radiation (LDR) are reported to induce transient changes in mouse lymphocytes, such as enhanced response to polyclonal T cell mitogens, increased expression of heat shock proteins, and p53. We evaluated the role of cell cycle proteins and apoptosis in lymphocytes of C57BL/6 mice exposed to 20 cGy fractionated LDR. We found an enhanced cell proliferation in response to the mitogen concanavalin A (con A). The expression of several cell cycle and apoptosis-related intracellular and extracellular proteins was analyzed by flowcytometry following labeling with specific antibodies. An increased response to con A was accompanied by an increase in the expression of proliferating cell nuclear antigen (PCNA) and cyclins D and A. The expression of cyclin B did not change significantly. In 20 cGy-exposed C57BL/6 mice, the caspase activity and apoptosis were reduced in con A-stimulated spleen cells as compared to sham controls. The expression of Fas and Fas ligand was analyzed by labeling with specific antibodies followed by flowcytometry. There was no change in the expression of Fas and Fas ligand. The change in the mitochondrial transmembrane potential was followed by labeling the cells with the dye 5,5',6,6',-tetrachloro-1,1,3,3-tetraethylbenzimidazolcarbocyanine iodide (JC-I) and analyzing by flowcytometry. Mitochondrial stability was increased in spleen cells of LDR-treated mice. These data suggest that LDR induces augmentation of mitogenic response by modulation of expression of cyclins and the mitochondrial membrane potential leading to reduced apoptosis.
Shankar
Bhavani
B
Immunology Section, Radiation Biology Health Sciences Division, Bhabha Atomic Research Centre, Modular Laboratories, Trombay, Mumbai, India.
Sainis
Krishna B
KB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D005720:Gamma Rays; D007425:Intracellular Membranes / Q000528:radiation effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects; D013601:T-Lymphocytes / Q000528:radiation effects*; D014916:Whole-Body Irradiation
D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D018809:Proliferating Cell Nuclear Antigen; D003208:Concanavalin A; D019938:Cyclin D1; D020169:Caspases