Rasey J S, Nelson N J, Larson S M
Eur J Cancer Clin Oncol. 1982 Jul;18(7):661-8. doi: 10.1016/0277-5379(82)90212-7.
The cytotoxicity of citrated gallium nitrate (NSC 15200) to EMT-6/UW mouse sarcoma cells growing in vitro was assayed as growth inhibition in treated cultures as well as cell survival (colony-forming ability) after acute or chronic exposure to graded doses. Gallium nitrate is both cytostatic and lethal to cells, with some growth inhibition occurring after chronic exposure to low doses (10 micrograms/ml) which kill essentially no cells. Cell kill and growth inhibition were both observed if cells were exposed for 24 hr or more to doses greater than 50 micrograms/ml. The growth inhibitory and lethal effects of gallium nitrate were enhanced by the addition of human transferrin to the medium. This enhanced toxicity was consistent with, and proportional to, the increased gallium uptake in the presence of transferrin rather than a direct effect of this iron transport protein. The addition of ferric citrate greatly reduced the toxic effect of the gallium salt. Cells in stationary plateau phase cultures appear to be as sensitive to gallium nitrate as exponentially growing cells. Ga3+ may mimic Fe3+ in some aspects of cellular metabolism, and competition between the two metals occurs at the initial uptake step, binding to transferrin, and possibly at other points in cell metabolism.
测定了柠檬酸硝酸镓（NSC 15200）对体外生长的EMT - 6/UW小鼠肉瘤细胞的细胞毒性，方法是检测处理后的培养物中的生长抑制情况以及急性或慢性暴露于分级剂量后细胞的存活情况（集落形成能力）。硝酸镓对细胞既有抑制生长的作用又有致死作用，在慢性暴露于低剂量（10微克/毫升）时会出现一些生长抑制，但基本上不会杀死细胞。如果细胞暴露于大于50微克/毫升的剂量24小时或更长时间，则会观察到细胞杀伤和生长抑制。向培养基中添加人转铁蛋白可增强硝酸镓的生长抑制和致死作用。这种增强的毒性与转铁蛋白存在时镓摄取增加一致且成比例，而不是这种铁转运蛋白的直接作用。添加柠檬酸铁大大降低了镓盐的毒性作用。处于静止平台期培养的细胞似乎与指数生长的细胞对硝酸镓一样敏感。Ga3 +在细胞代谢的某些方面可能模拟Fe3 +，并且这两种金属在初始摄取步骤、与转铁蛋白结合以及可能在细胞代谢的其他点存在竞争。
