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目的用3个遗传终点来评价人外周血淋巴细胞暴露于不同剂量长春新碱(VCR)后的遗传损伤。方法外周血来自男女2名助血员,用终浓度为0.00(溶剂对照)、0.01、0.02、0.04、0.08μg/ml的VCR染毒24h,再用微核试验、彗星试验和hprt基因突变试验检测淋巴细胞的遗传损伤。微核试验以微核率、微核细胞率、核芽、核质桥、核分裂指数和凋亡细胞作为染色体损伤指标;彗星试验以平均尾长和平均尾相作为DNA损伤的指标;hprt基因突变试验以基因突变率作为评价指标。结果3种试验均呈阳性。hprt基因突变率和凋亡细胞数从0.02μg/ml剂量开始与对照的差异有统计学意义(P<0.05或P<0.01),其余指标从最低剂量组开始就明显高于对照组,差异均有统计学意义(P<0.01或P<0.05),并存在剂量-效应关系。结论VCR在体外可通过不同机制诱发人淋巴细胞的遗传损伤。
Objective To evaluate the genetic damage of human peripheral blood lymphocytes exposed to different doses of vincristine (VCR) using three genetic endpoints. Methods Peripheral blood was collected from two male and female blood donors. The cells were exposed to VCR at 0.01, 0.02, 0.04 and 0.08 μg / ml for 24 h at final concentrations of 0.00 (solvent control), and then subjected to micronucleus test, comet assay and hprt gene mutation test Detection of lymphocyte genetic damage. In micronucleus test, micronucleus rate, micronucleus rate, nuclear buds, nucleolus bridge, mitotic index and apoptotic cells were used as indexes of chromosome damage. Average tail length and average caudal phase were used as indexes of DNA damage in the comet assay. Mutations of hprt gene The rate of gene mutation as a test indicator. Results 3 kinds of tests were positive. The mutation rate of hprt gene and the number of apoptotic cells were significantly different from the control at 0.02μg / ml dose (P <0.05 or P <0.01). The other indexes were significantly higher than those in the lowest dose group There was statistical significance (P <0.01 or P <0.05), and there was a dose-response relationship. Conclusion VCR can induce genetic damage of human lymphocytes through different mechanisms in vitro.