1. Protective Effects of Cimetidine on Radiation-induced Micronuclei and Apoptosis in Human Peripheral Blood Lymphocytes
- Author
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Yasuo Kojima, Takashi Kondo, Miki Shoji, Ryusuke Futatsuya, and Qing-Li Zhao
- Subjects
Adult ,Male ,Apoptosis ,Radiation-Protective Agents ,Radiation induced ,Pharmacology ,Biochemistry ,Chromosomes ,Flow cytometry ,medicine ,Humans ,Lymphocytes ,Cimetidine ,Receptor ,Micronuclei, Chromosome-Defective ,Chromosome Aberrations ,Micronucleus Tests ,medicine.diagnostic_test ,Caspase 3 ,Chemistry ,Antagonist ,Dose-Response Relationship, Radiation ,General Medicine ,Glutathione ,Peripheral blood ,Gamma Rays ,Caspases ,Micronucleus test ,Female ,medicine.drug - Abstract
The radioprotective effects of cimetidine, which has been used clinically as an antagonist of H2 receptor, on radiation-induced micronuclei and apoptosis in human peripheral blood lymphocytes (PBL) prepared from healthy donors were studied. Cells were treated with cimetidine before or after X-irradiation, and then cytokinesis-blocked micronucleus assay and flow cytometry for measurement of phosphatidylserine externalization were utilized to evaluate the radiation-induced cytogenetic damage and apoptosis. The protective effect of preirradiation treatment of cimetidine on radiation-induced micronuclei was dependent on the concentration. The maximum protection rates of cimetidine (1 mM) on frequencies of micronuclei were 38.8 and 30.2% for cells treated before and after X-irradiation (5 Gy), respectively. Protective effects of pre- and post-irradiation treatment with cimetidine on radiation-induced early apoptosis and decreased activity of caspase-3 were observed. A study of electron paramagnetic resonance-spin trapping with 5,5'-dimethyl-1-N-oxide revealed that the rate constant of cimetidine with radiation-induced OH radicals is about 4.5 x 10(9) l/mol/s. Cimetidine did not significantly increase the intracellular concentration of glutathione. These results suggest that cimetidine suppresses radiation-induced micronuclei and apoptosis via OH radical scavenging and an intracellular antioxidation mechanism. Cimetidine appears to be a useful candidate for the future development of post-irradiation radioprotectors.
- Published
- 2002
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