Inhibition of lead chromate clastogenesis by ascorbate: relationship to particle dissolution and uptake.
Inhibition of lead chromate clastogenesis by ascorbate: relationship to particle dissolution and uptake.
复制标题
抗坏血酸对铬酸铅断裂发生的抑制：与颗粒溶解和吸收的关系。
DOI：
10.1093/carcin/14.3.429
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发表时间：
1993
期刊：
影响因子：
4.7
通讯作者：
Patierno,SR
中科院分区：
文献类型：
--
作者：
Wise,JP;Orenstein,JM;Patierno,SR
金属铬盐被认为是人类的致癌物质，特别是低溶解度的盐。铬酸铅是一种高度不溶的金属铬盐，已被证明具有致癌、遗传毒性和致分裂作用。本文研究了颗粒-细胞接触、颗粒溶解和颗粒摄取在铬酸铅碎裂活性中的作用。用Pb51CrO4研究发现，铬酸铅颗粒(平均直径1.2μm，表面电荷-28 mV)在水中稍有溶解，当颗粒在培养液中孵育时，溶解度增加2倍，但加入血清不会进一步增加溶解度。铬酸铅与中国仓鼠卵巢(CHO)细胞共同孵育时，胞外铬浓度是单独培养时的7倍。在CHO细胞暴露于致分裂剂量的铬酸铅后，细胞内离子铬浓度以剂量依赖的方式增加，估计水平高达每细胞1.2 mm。在无毒剂量的维生素C存在的情况下，用铬酸铅颗粒处理细胞，可以阻止离子铬的摄取，并消除颗粒的碎裂活性。透射电子显微镜显示，铬酸铅颗粒在短短1h内就被CHO细胞内化到吞噬空泡中，与维生素C共处理对内化作用无明显影响。这些数据表明，虽然发生了吞噬颗粒摄取，但颗粒-细胞接触和细胞外溶解是铬酸铅产生断裂活性的原因。这些数据还表明，颗粒六价铬酸盐的遗传毒性可以被维生素C阻断。
Chromium metal salts are considered to be human carcinogens, especially the salts of low solubility. Lead chromate, a highly insoluble chromium metal salt, has been shown to be tumorigenic, genotoxic and clastogenic. In this study, the roles of particle—cell contact, particle dissolution and particle uptake in the clastogenic activity of lead chromate were investigated. Using Pb51CrO4it was found that lead chromate particles (1.2 μm mean diameter, -28 mV surface charge) were slightly soluble in water; solubility increased 2-fold when particles were incubated in culture medium, but was not increased further by the addition of serum. The extracellular concentration of chromium increased 7-fold when lead chromate was incubated in the presence of Chinese hamster ovary (CHO) cells compared with culture medium alone. The intracellular concentration of ionic chromium increased in a dose-dependent manner following exposure of CHO cells to clastogenic doses of lead chromate reaching estimated levels as high as 1.2 mM per cell. Treatment of cells with lead chromate particles in the presence of a nontoxic dose of vitamin C blocked uptake of ionic chromium and eliminated the clastogenic activity of the particles. Transmission electron microscopy showed that lead chromate particles were internalized by CHO cells in phagocytic vacuoles in as little as 1 h; internalization was unaffected by co-treatment with vitamin C. It was demonstrated that particle—cell contact was required for lead chromate-induced clastogenesis. These data show that although phagocytic particle uptake occurs, particle—cell contact and extracellular dissolution are responsible for the clastogenic activity of lead chromate. These data also demonstrate that the genotoxicity of particulate hexavalent chromates can be blocked by vitamin C.