低剂量辐射对环磷酰胺化疗毒性作用的影响

Effects of low dose pre-irradiation on the toxicity of cyclophosphamide

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose y-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 close 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 y-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 sig-nificance (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 y-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-close chemotherapy. 2. A 75 mGy y-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-close CTX chemotherapy can cause DNA damage of peripheral lymphocytes; 75 mGy y-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 y-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.