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PURPOSE: This study uses a radiation chemistry approach to determine if DNA is an important target for radiation-induced apoptosis of myc (MR4) and myc plus ras (3.7) transfected rat embryo fibroblast cell lines. MATERIALS AND METHODS: The radiation protection efficiency of four thiols was compared with net molecular charge ranging from -1 to +2: mercaptopropionic acid (Z= -1), mercaptoethanol (Z=0), cysteamine (Z= +1), N(2-mercaptoethyl)-1,3-diaminopropane (Z= +2). Protection factors were determined for these thiols against radiation-induced apoptosis (Apoalert assay), mitotic cell death (clonogenic assay) and double-strand break (dsb) induction (pulse field gel electrophoresis) in MR4 and 3.7 cells. Theoretical protection factors for these thiols against dsb induction were also calculated from second-order chemical repair constants for single-strand breaks (ssb) and the concentration of added thiols in MR4 and 3.7 cell lines. RESULTS: The charge-dependent increases observed for measured protection factors against radiation-induced apoptosis did not differ significantly between the two cell lines, nor did they differ significantly from the corresponding increases observed for radiation-induced mitotic cell killing and for induction of dsb. The calculated protection factor for dsb also showed a thiol charge-dependent increase similar to the measured protection factors for all of the other parameters studied. CONCLUSIONS: These results are consistent with the hypothesis that DNA is an important target for radiation-induced apoptosis.

Type

Journal article

Journal

Int J Radiat Biol

Publication Date

03/2000

Volume

76

Pages

343 - 354

Keywords

Animals, Apoptosis, Cell Line, Cell Survival, Colony-Forming Units Assay, Cytoprotection, DNA, DNA Damage, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Embryo, Mammalian, Fibroblasts, Free Radical Scavengers, Genes, myc, Genes, ras, Intracellular Fluid, Radiation-Protective Agents, Rats, Sulfhydryl Compounds, Transfection