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.