小剂量电离辐射引起体细胞染色体不分离及其与拓扑异构酶Ⅱα的关系

Effects of low dose radiation on chromosome non-disjunction and the relation with topoisomerase Ⅱα

探讨小剂量电离辐射对体细胞染色体不分离的影响,及与DNA拓扑异构酶Ⅱα(TopoisomeraseⅡα,TOPOIIα)的关系。用137Csγ为辐射源与中期染色体计数法,研究了小剂量照射与人外周血淋巴细胞有丝分裂染色体不分离关系,发现照射对染色体不分离的影响具剂量效应、时间效应和次数累加效应;用Western blot和RT-PCR检测了照射对Hela细胞中TOPOIIα表达的影响,也存在剂量效应、时间效应和次数累加效应;以TOPOIIα抑制剂(VP-16)抑制Hela细胞中TOPOIIα活性,也引起Hela细胞有丝分裂染色体不分离率增加,照射和抑制TOPOIIα活性的协同作用加重对不分离的影响。结果提示TOPOⅡα表达的变化是小剂量照射引起有丝分裂染色体不分离的机制之一。

To explore the effect of low dose radiation on chromosome non-disjunction, human lymphocyte were cultured and treated with 137^Cs γ,-ray （≤5Gy） and the metaphase chromosomes were counted. The results showed that the rate of aneuploid and hyperdiploid increased markedly after irradiation, and was dose-dependent and time-dependent. RT-PCR and Western blot were used to study changes of TOPOⅡα expression in the irradiated HeLa cells. A transient and significant decrease of TOPOⅡα after 5 Gy irradiation was detected： the decrease began at 4h after irradiation, reached to the lowest level at 12h, and began to return at 16h. The decreasing rate increased with the irrdiation dose, and decreasing rate was higher with multiple irradiations than a single irradiation of the same dose. The decrease of TOPOⅡα after irradiation was also time- and dose-dependent. The rate of aneuploid and hyperdiploid increased more significantly in Hela cells under the co-effect of TOPOⅡα inhibitor （VP-16） and irradiation. The results suggest that low dose irradiation may causes chromosome non-disjunction, and its mechanism is related with the change of TOPOⅡα expression.