Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes
An early event in death of interphase lymphocytes exposed in vivo or in vitro to low doses of gamma-irradiation is the degradation of DNA into nucleosome-sized fragments. Induction of fragmentation required RNA and protein synthesis because actinomycin D and cycloheximide, respectively, are able to inhibit DNA fragmentation in irradiated lymphocytes. Studies adding cycloheximide and actinomycin D at various times postirradiation suggest that once the metabolic process is initiated within an individual cell it proceeds to completion. The reversible RNA synthesis inhibitor, 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole inhibits DNA fragmentation in irradiated thymocytes. When this drug is removed after 6 hr, irradiated thymocytes proceed to fragment their DNA; this suggests that an inducing signal that is not simply mRNA persists within the irradiated cell for at least 6 hr after irradiation. In contrast to mitogen-activated T and B lymphoblasts, resting T and B cells show significant DNA fragmentation after exposure to 100 to 500 rad. At 2000 rad, all of the splenic subpopulations die rapidly via a different mechanism. By studying the mechanism of DNA fragmentation induced during the interphase death of lymphocytes, we hope to understand better the extreme sensitivity of resting lymphocytes to radiation and what may be the common final pathway of programmed cell death.
- Research Organization:
- Univ. of Colorado School of Medicine, Denver
- OSTI ID:
- 5650838
- Journal Information:
- J. Immunol.; (United States), Vol. 139:10
- Country of Publication:
- United States
- Language:
- English
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DNA
GENETIC RADIATION EFFECTS
LYMPHOCYTES
RADIOSENSITIVITY
GAMMA RADIATION
GENE REGULATION
MICE
RADIATION DOSES
RNA
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DOSES
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
IONIZING RADIATIONS
LEUKOCYTES
MAMMALS
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NUCLEIC ACIDS
ORGANIC COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RODENTS
SOMATIC CELLS
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560120* - Radiation Effects on Biochemicals
Cells
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