低剂量辐射对环磷酰胺化疗毒性作用的影响(英文)

来源 :Chinese-German Journal of Clinical Oncology | 被引量 : 0次 | 上传用户:xuxu517
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Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy. Objective: The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage, DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide (CTX). Methods: Kunming strain male mice were randomly divided into five groups: control group, sham-irradiated group, low dose irradiation group (LDR group), cyclophosphamide chemotherapy group (CTX group) and low dose irradiation combined with chemotherapy group ). Having been raised for one week, all the mice were implanted subcutaneously with S180 cells in the left inguen (control group excluded). On days 8 and 11, mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ -irradiation, 30 h later mice of CTX and LDR + CTX groups were injected ip 3.0 mg cyclophosphamide. All mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis (SCGE); ALT activity, total MDA content, SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry; genetic material damage was analyzed using micronucleus frequency (MNF) of polychromatoerythrocytes (PCE) in bone marrow. Results: 1. Differences of MDA contents, SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance (P <0.01); in control group MDA content was the lowest, SOD and GSH -PX activity were the highest, while in CTX group MDA content was the lowest, while SOD and GSH-PX activity were the highest; while with CTX group MDA content was the lowest; P <0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance (F = 1.262, P> 0.05) .Differences of TP and ALB of plasma between 5 groups had statistical significance (F = 12.879 and 6.336 respecti vely, P <0.01); TP and ALB in control groups were higher than those of other groups and compared with sham-irradiated groups, TP and ALB in LDR group elevated significantly (P <0.05). 3. Differences of DNA damage of peripheral DNA damage in control group was the lightest, while DNA damage in CTX group was the severest; compared with CTX group, DNA damage in LDR + CTX group was much lighter (F = 6.383, P <0.01) P <0.05) .4. MNF of PCE between 5 groups had remarkable significance (F = 179.652, P <0.01); compared with control group and sham-irradiated group, MNF in CTX group increased significantly CTX group, MNF in LDR + CTX group had a tendency of decline, which had no statistical significance (P> 0.05) .Conclusion: 1.CTX can damage the hepatic tissue through oxidative stress; 75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes, promote elimination of free radicals, so as to alleviate the damagin g effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy. 2. A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma, but may have protective effect on the protein synthesis function of liver.3 . High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes; 75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage. 4. CTX has potent mutagenic effect, can cause significant increase of MNF of PCE; 75 mGy γ -ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.
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