低剂量辐射对环磷酰胺所致小鼠DNA及遗传物质损伤的影响(英文)

EFFECT OF LOW DOSE PRE-IRRADIATION ON GENETIC MATER-ICAL DAMAGE CAUSED BY HIGH DOSAGE OF CYCLOPHOSPHAMIDE

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-radiation on damages of DNA in peripheral lymphocytes and genetic material due to high-dose cyclophosphamide （CTX）. Methods Fifty-five Kunming strain male mice were randomly divided into five groups： blank group, sham radiation group, low-dose radiation group （LDR group）, cyclophosphamide chemotherapy group （CTX group） and LDR＋CTX group. Having being raised for one week, all the mice （blank group excluded） were implanted subcutaneously with S180 cells in the left groin. On day 8 and 11, mice in LDR and LDR＋CTX groups were given 75 mGy whole body γ radiation, 30 hours later, mice in CTX and LDR＋CTX groups were given intraperitoneal injection of 3.0 mg cyclophosphamide. All the mice were sacrificed on day 13. DNA damage was analyzed using single cell gel electrophoresis, genetic material damage of bone marrow was analyzed using micronucleus frequency （MNF） of polychromatoerythrocytes （PCE）. Results Compared with sham radiation group, the DNA damage in CTX group increased significantly; 75 mGy γ-ray pre-radiation signifi- cantly decreased the DNA damage induced by CTX. Compared with control group and sham-irradiation group, MNF of PCE in CTX group increased markedly （t 3.63 5. 46,P（0.05） ; pre-radiation lessened MNF of PCE, but with no statistically significant （P〉0.05）. Conclusion High dose CTX may cause damage of DNA in peripheral lymphocytes, which may be prevented by 75 mGy-radiation prior to chemotherapy. CTX has a strong mutagenic action leading to dramatic increase of MNF in bone marrow. 75 mGy γ-ray pre-radiation fails to inhibit the genetic toxicity induced by high-dose CTX chemotherapy.