砷对大鼠肢芽细胞增殖和分化的影响

Influence of Arsenic on Proliferation and Differentiation of Rat Bud Cells in Vitro

为了进一步阐明三氧化二砷的发育毒性，本研究应用Ｆｌｉｎｔ等人建立的胚胎肢芽细胞微团培养法，探讨了不同浓度砷对体外培养的ＳＤ大鼠胚胎肢芽细胞增殖和分化的影响。结果表明砷对大鼠肢芽细胞的增殖和分化均有抑制作用，呈明显的剂量－反应关系；砷对肢芽细胞的５０％增殖抑制浓度（ＩＰ５０）和５０％分化抑制浓度（ＩＤ５０）分别为０．７０ｍｇ／Ｌ和０．２１ｍｇ／Ｌ；ＩＰ５０／ＩＤ５０值为３．３，揭示砷对大鼠肢芽细胞分化的影响要远大于对细胞增殖的影响。根据Ｒｅｎａｕｌｔ等人推荐的体外致畸判断标准，砷属于强致畸物。实验结果提示砷对大鼠肢芽细胞分化的抑制作用可能并非其细胞毒性作用所致，这是砷致畸作用的重要基础之一。此外还初步探讨了大鼠肢芽细胞异常分化的分子机制。

he objective of this study was designed to evaluate the developmental toxicity of arsenic and its effect on embryonic chondrogenesis of SpragueDawley rat by using Flint's rat limb bud cell micromass cultrure system in vitro. The results revealed that arsenic inhibited markedly both proliferation and differentiation of rat limb bud cells in vitro and there was an obvious doseresponse relationship. The concentrations of arsenic for IP50 (dose of inhibiting proliferation by 50% of the control value) and ID50 (dose of inhibiting differentiation by 50% of the control value) were 070mg/L and 0.21 mg/L respectively. The ratio between IP50 and ID50 was 33. These parameters indicated that the influence of arsenic on differentiation of rat limb bud cells was stronger than on proliferation, and arsenic belonged to a strong teratogenic agent and a specific inhibitor. This study suggested that the specific inhibitory action of arsenic on limb bud cell differentiation did not result from the cytotoxicity, but would result from the teratogenic effects of arsenic.