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损伤及遗传物质损伤的影响。方法昆明种雄性小鼠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)。常规饲养1周后,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和11天对LDR组和LDR+CTX组小鼠给予75mGy-γ射线全身照射,照射后30h分别给予CTX组和LDR+CTX组小鼠腹腔注射环磷酰胺3.0mg;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;采用骨髓嗜多染红细胞微核率(MNF)检测遗传物质损伤。结果①环磷酰胺化疗后DNA损伤程度较空白对照及荷瘤对照组均显著增加;环磷酰胺化疗前给予75mGy-γ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。②大剂量环磷酰胺化疗后小鼠骨髓嗜多染红细胞微核率较空白对照组及单纯荷瘤组有显著增加(P〈0.01);环磷酰胺化疗前给予75mGy-γ射线照射则可降低环磷酰胺所致微核率的增加,但差异无统计学意义(P〉0.05)。结论①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75mGy-γ射线照射对DNA损伤可能产生一定的保护作用。②环磷酰胺有强大的致突变作用,可导致骨髓嗜多染红细胞微核率显著增加,75mGy-γ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-rays pre-irradiation on the induction of DNA damage and genetic material damage in peripheral lymphocytes by high dosage of cyclophosphamide (CTX). Methods Male Kunming strain mice were randomly divided into five groups: control group, sham-irradiated group, low dose irradiated group( LDR group), cyclophosphamide chemotherapy group( CTX group) and low dose irradiation combined with chemotherapy group( LDR + CTX group). After being feeded for one week, all the mice were implanted subcutaneously with S180 cells in the left groin (control group excluded). On days 8 and 11, groups of LDR and LDR + CTX were administered with 75 mGy of whole-body irradiation, 30 h later groups CTX and LDR + CTX were injected intraperitoneally 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). Genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow. Results (1) Compared with control group and sham-irradiated group, the DNA damage of peripheral lymphocytes in CTX group were increased significantly ( P 〈 0.01 ) ; 75 mGy pre-irradiation might decreased the DNA damage induced by chemotherapy significantly. (2) Compared with control group and shamirradiated group, MNF of PCE in CTX group increased significantly( P 〈 0.01 ), while 75 mGy pre-irradiation had a tendency to decline on MNF of PCE, but without statistical significance( P 〉 0.05 ). Conclusions (1) Highdosage of CTX chemotherapy can cause DNA damage in peripheral lymphocytes. 75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage. (2) CTX has potent mutagenic effect, giving remarkable rise to MNF of PCE. 75 mGy γ-ray pre-irradiation has not obvious protection against genetic toxicity of high-dose CTX chemotherapy.