Elias Z, Poirot O, Schneider O, Marande A M, Danière M C, Terzetti F, Pezerat H, Fournier J, Zalma R
Department of Experimental Industrial Toxicology, National Institute of Research and Security (INRS), Vandoeuvre, France.
Cancer Detect Prev. 1995;19(5):405-14.
Four physicochemically characterized iron-containing minerals, one fibrous (a nemalite [brucite]) and three nonfibrous (a biotite [phyllosilicate], a magnetite (Fe3O4), and a goethite [FeOOH alpha]), were studied for cytotoxicity and morphological transformation of Syrian hamster embryo (SHE) cells. When colony-forming efficiency was used as a measure of cytotoxicity, it appeared that the nemalite was about 1.7-fold more cytotoxic than the biotite and magnetite. However, if the inhibitory effect on the cell growth was considered the nemalite appeared to be 8-fold more effective. The analysis of the cell cycle kinetics by flow cytometry revealed a time- and dose-dependent delay in the progression of cells through the cell cycle, with the accumulation of cells in S and G2-M phases, more particularly in the cultures treated with nemalite. While the goethite was neither cytotoxic nor transforming, the other three dusts were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. According to their transforming potency they ranged as follows: nemalite > biotite > magnetite. A 18-fold higher treatment concentration of magnetite than that of nemalite was necessary to induce the same transformation frequency. The iron chelator desferrioxamine abolished the transforming effect of nemalite. The results suggest that (i) the cytotoxicity and the transformation are induced by some divalent iron-containing minerals and that they are two distinct processes; (ii) there is a varying ability among these dusts to induce cell transformation; and (iii) the bioavailability of divalent iron leading to formation of reactive iron-oxygen species could mediate the transforming potency of a mineral. Physicochemical studies correlated to biological effects of many metallic mine dusts are the only approach for understanding their mechanisms of action and their role in occupational pathology.
研究了四种经过物理化学特性表征的含铁矿物质，一种为纤维状（一种硅镁石[水镁石]），三种为非纤维状（一种黑云母[层状硅酸盐]、一种磁铁矿（Fe3O4）和一种针铁矿[α-FeOOH]）对叙利亚仓鼠胚胎（SHE）细胞的细胞毒性和形态转化。当将集落形成效率用作细胞毒性的衡量指标时，硅镁石的细胞毒性似乎比黑云母和磁铁矿高约1.7倍。然而，如果考虑对细胞生长的抑制作用，硅镁石的效果似乎高8倍。通过流式细胞术对细胞周期动力学的分析显示，细胞在细胞周期进程中存在时间和剂量依赖性延迟，细胞在S期和G2-M期积累，尤其是在用硅镁石处理的培养物中。虽然针铁矿既无细胞毒性也无转化作用，但其他三种粉尘以剂量依赖性方式有效地诱导了SHE细胞的形态转化。根据它们的转化能力，排序如下：硅镁石>黑云母>磁铁矿。要诱导相同的转化频率，磁铁矿的处理浓度需要比硅镁石高18倍。铁螯合剂去铁胺消除了硅镁石的转化作用。结果表明：（i）细胞毒性和转化是由一些含二价铁的矿物质诱导的，且它们是两个不同的过程；（ii）这些粉尘诱导细胞转化的能力各不相同；（iii）导致活性铁氧物种形成的二价铁的生物利用度可能介导了一种矿物质的转化能力。将物理化学研究与许多金属矿尘的生物学效应相关联是理解其作用机制及其在职业病理学中作用的唯一途径。
