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目的研究低剂量γ射线预照射对大剂量环磷酰胺化疗所致外周血淋巴细胞DNA及遗传物质损伤的影响。方法昆明种雄性小鼠55只,随机分为空白对照组、荷瘤对照组(假照组)、荷瘤低剂量照射组(LDR组)、荷瘤环磷酰胺化疗组(CTX组)和荷瘤低剂量照射联合化疗组(LDR+CTX组)。小鼠常规饲养7 d后于左腹股沟皮下各接种S180肉瘤细胞(空白对照组除外),接种后第8、11天LDR组和LDR+CTX组小鼠给予75 mGyγ射线全身照射,照射30 h后分别给予CTX组和LDR+CTX组小鼠腹腔注射环磷酰胺3.0 mg,第13天处死所有小鼠,分别取血,采用单细胞凝胶电泳法检测外周血淋巴细胞DNA损伤情况;采用骨髓嗜多染红细胞微核率(MNF)检测遗传物质损伤情况。结果环磷酰胺化疗后DNA损伤程度较空白对照及假照组均显著增加;环磷酰胺化疗前给予75 mGyγ射线照射则可显著降低大剂量环磷酰胺化疗所致的DNA损伤。大剂量环磷酰胺化疗后小鼠骨髓MNF较空白对照组及单纯荷瘤组有显著增加(t=3.63~5.46,P<0.05);环磷酰胺化疗前给予75 mGyγ射线照射则可降低环磷酰胺所致微核率的增加,但差别无统计学意义(P>0.05)。结论大剂量环磷酰胺化疗可引起外周血淋巴细胞DNA损伤;化疗前给予75 mGyγ射线照射对DNA损伤可能产生一定的保护作用。环磷酰胺有强大的致突变作用,可导致骨髓MNF显著增加,75 mGyγ射线预照射对大剂量环磷酰胺化疗的遗传学毒性未表现出明显的保护作用。
Objective To study the effect of low dose γ-ray pre-irradiation on the DNA and genetic material damage of peripheral blood lymphocytes induced by high-dose cyclophosphamide chemotherapy. Methods Fifty-five Kunming male mice were randomly divided into blank control group, tumor-bearing control group (sham group), low-dose group (LDR group), tumor-bearing CTX group Low dose radiation combined with chemotherapy group (LDR + CTX group). The mice were inoculated with S180 sarcoma subcutaneously in the left groin for 7 days (except for the blank control group). The mice in the LDR + LDH + CTX group were given 75 mGy γ-ray irradiation on the 8th and 11th day after inoculation. After irradiation for 30 hours The mice in CTX group and LDR + CTX group were intraperitoneally injected with 3.0 mg cyclophosphamide, all the mice were sacrificed on the 13th day, and the blood was collected respectively. The DNA damage of peripheral blood lymphocytes was detected by single cell gel electrophoresis. Multi-RBC micronucleus test (MNF) to detect genetic material damage. Results DNA damage after cyclophosphamide chemotherapy was significantly increased compared with blank control group and sham group; 75 mGy gamma irradiation before cyclophosphamide treatment significantly reduced DNA damage induced by high dose cyclophosphamide chemotherapy. Compared with blank control group and simple tumor-bearing group, the MNF of mice bone marrow increased significantly after high-dose cyclophosphamide chemotherapy (t = 3.63-5.46, P <0.05); while cyclophosphamide administration of 75 mGy γ-rays before chemotherapy decreased the content of cyclic phosphorus Amide micronucleus rate increased, but the difference was not statistically significant (P> 0.05). Conclusion High-dose cyclophosphamide chemotherapy can cause DNA damage in peripheral blood lymphocytes. Pretreatment with 75 mGy γ-ray irradiation may have a protective effect on DNA damage. Cyclophosphamide has a strong mutagenic effect, can cause a significant increase in bone marrow MNF, 75 mGy gamma ray pre-irradiation for high-dose cyclophosphamide chemotherapy genetic toxicity showed no significant protective effect.