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OBJECTIVE： To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS： Healthy male Beagle dogs were randomly divided into normal control group， model control group， positive drug group （lentinan， 21.33 mg/kg） and cimetidine low-dose， medium-dose and high-dose groups （5.33， 10.67， 21.33 mg/kg）， with 4 Beagle dogs each. Except for normal control group， other groups were given 60Co-γ accumulative irradiation （dosage rate： 0.040 8 mGy/min） for 23 d； the medication groups were given relevant medicine orally before irradiation， once a day. Twenty-four hours after stopping irradiation， TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins （Bax， Bcl-2， Caspase-3， p53） in liver tissue was detected by immunohistochemistry. RESULTS： Compared with normal control group， apoptotic cells and Bax， Caspase-3， p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group； the percentage of apoptotic cells， protein expression levels of Bax， Caspase-3 and p53 were increased significantly； Bcl-2 positive cells were decreased significantly， and its protein expression level was decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups； the percentage of apoptotic cells and protein expression levels of p53 in medication groups， protein expression levels of Bax in positive drug group， cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly； protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group （P＜0.05 or P＜0.01）. CONCLUSIONS： Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs， and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax， Caspase-3 and p53 in liver cells.
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Objective To investigate the protective effects of cimetidine on rats with low dose rate (LDR) 60Co γ-ray cumulative irradiation. Methods Sixty male SD rats (6-8 weeks old) were randomized into 6 groups (10 each): normal control group, model group, positive control group (89.0 mg/kg lentinan), low-dose cimetidine group (23.3 mg/kg cimetidine), medium-dose cimetidine group (70.0 mg/kg cimetidine), and high-dose cimetidine group (210.0 mg/kg cimetidine). Except for rats in normal control group, the rest rats were irradiated with 60Coγ-ray to a cumulative dose of 0.5 Gy with a dose rate of 3.228 mGy/ h. Twenty-four hours after the last irradiation, peripheral blood cells, bone marrow DNA content, frequencies of micronucleated polychromatic erythrocytes (fMNPCE), bone marrow nucleated cells, sperm count, testis HE, sex hormones, superoxide dismutase (SOD), glutathione (GPx), catalase (CAT) activity, and malondialdehyde (MDA) content were measured. Results Compared with normal control group, in model group, WBC, lymphocyte and granulocyte content, bone marrow DNA content and the number of nucleated cells significantly decreased (P<0.05), but fMNPCE increased significantly (P<0.01). In addition, sperm count, testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels significantly reduced (P<0.05 or P<0.01), estradiol (E2) levels significantly increased (P<0.05), SOD, GPx and CAT activities significantly decreased (P<0.05 or P<0.01), and MDA levels significantly increased (P<0.01). Rat models were established successfully. Compared with model group, in positive control group, the bone marrow DNA content and T content significantly increased (P<0.05), antioxidant enzyme activity of SOD, GPx and CAT significantly increased (P<0.05 or P<0.01), while the contents of fMNPCE, MDA and E2 significantly reduced (P<0.05 or P<0.01). In the cimetidine-treated groups, the blood lymphocyte number and bone marrow DNA content significantly increased (P<0.01), the activity of antioxidant enzymes SOD, CAT, GPx, T, FSH and LH increased, and the content of fMNPCE, E2 and MDA decreased, the damage of testicular tissue structure decreased (P<0.05), and the number of sperm increased, but there has no statistic significance. Conclusion Cimetidine, as a potential radiation protection drugs, could effectively improve the rat injury with low-dose-rate 60Coγ-ray cumulative irradiation.
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Objective To investigate the biological effect of 125I seeds continuous low dose rate (CLDR) irradiation and 60Co γ-ray high dose rate (HDR) irradiation on H1299 cell line of non-small cell lung cancer (NSCLC). Methods H1299 cells in exponential growth were separately irradiated with 125I seeds CLDR irradiation and 60Co γ-ray HDR irradiation. The cell survival fraction was inspected with clone formation experiment, the cell cycle and apoptosis rate was determined with flow cytometry, and the expressions of Bax and Bcl-2 proteins were measured by Western blot method. Results With the irradiation dose increasing, the anti-proliferation effect of 125I seeds CLDR irradiation on H1299 cells became more remarkable than that of 60Coγ-ray HDR irradiation. When the irradiation dose reached 4 Gy, the G2/M phase percentage and the apoptotic ratio of H1299 cells in 125I seeds CLDR irradiation group were 21.77±0.31%and 13.79±0.50% respectively, which were only 18.85±0.99% and 8.79±0.22% respectively in 60Co γ-ray HDR irradiation group, the difference was statistically significant (P<0.05). In 125I seeds CLDR irradiation group the expression of Bax protein was remarkably up-regulated, while the expression of Bcl-2 protein was down-regulated. Conclusion The inhibition effect of 125I seeds CLDR internal irradiation on the proliferation of H1299 cells is more obvious than that of 60Co γ-ray HDR irradiation. In 125I seeds CLDR irradiation group, the imbalance of Bcl-2/Bax ratio may play an important role in achieving the antitumor effect.
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Objective To investigate the radiosensitivity enhancement on CL187 cancer cell lines after continous low-dose-rate irradiation of 125I seeds blocked by EGFR antibody.Methods There were control group,the irradiation or plus EGFR antibody group,with 3 samples in each group.Clongenic assay was used to detect the survival of cells.The cell cycle distribution and apoptosis were analyzed by flow cytometry.Results The survival fraction of CL187 cells were lower after blocked by EGFR antibody at the same dose irradiation.The SER were 1.34,1.59 and 1.98 when the antibody concentration were 2,5 and 10 nmol/L,respectively.The irradiation plus antibody led to more apoptosis(39.86%±4.38%)of CL187 cells than the irradiation (21.57%±2.97%)plused antibody(12.49%±1.59%)worked alone.Comparison of the low dose rate irradiation related to G2/M cell cycle arrest(46.41%±4.48%),More G1 cell cycle arrest(84.51%±3.42%)walked together along with the EGFR antibody.Conclusions EGFR antibody could enhance the cell radiosensitivity after continuous low-dose-rate.irradiation.The cell cycle redistribution and apoptosis might be the main mechanism of the radiosensitivity enhancement.