Comparative studies on cytotoxicity of micropollutants in water: Principle of cytotoxicity matrix

H. Utsumi, K. Kiyoshige, S. Shimbara, A. Hamada
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引用次数: 6

Abstract

Cytotoxicities were investigated with chemicals including pesticides, industrial materials, and chlorination by-products using colony formation inhibition of L-929 cells and membrane damage of “liposomes” to develop the simple bioassays for estimation of human hazardous micropollutants in water. Some chemicals including pesticides and chlorination by-products strongly inhibited colony formation of L-929 cells, and the inhibition was dose dependent. But most cytotoxic substances did not increase membrane permeability of liposomes, suggesting that Cytotoxicity of these chemicals does not arise from direct damage of cell membranes. The IC10 and IC50,10 and 50% inhibition concentrations, were obtained from the dose-response curve of colony formation. The IC10 showed good correlation (r = 0.75) to LD50 of rat by intraperitoneal administration but not to those by oral administration. The results were compared to those with viability of HL-60 cells, phagocytic activity of mice peritoneal macrophages, glycogenolysis, and LDH release of rat liver hepatocytes. The susceptibilities were largely different among these Cytotoxicity tests, and the colony formation inhibition test gave similar results to the viability of HL-60 cells. The principle of “cytotcxicity matrix” was developed from the comparison of cytotoxicities for each chemical. The characteristic relation was found between the chemical structure and the pattern of the Cytotoxicity matrix, indicating that the Cytotoxicity matrix may be useful for predicting the origin and nature of micropollutants. © 1994 by John Wiley & Sons, Inc..
水中微污染物细胞毒性的比较研究:细胞毒性基质原理
通过对L-929细胞集落形成的抑制和脂质体的膜损伤,研究了化学物质(包括杀虫剂、工业材料和氯化副产物)对细胞的毒性,建立了简单的生物测定法来估计水中对人体有害的微污染物。农药和氯化副产物等化学物质对L-929细胞集落形成有较强的抑制作用,且抑制作用具有剂量依赖性。但大多数细胞毒性物质不增加脂质体的膜通透性,提示这些化学物质的细胞毒性不是由直接破坏细胞膜引起的。根据菌落形成的量效曲线,得到IC10和IC50,即10%和50%的抑制浓度。IC10与腹腔给药大鼠LD50呈良好的相关性(r = 0.75),与口服给药大鼠无显著相关性。将结果与HL-60细胞活力、小鼠腹腔巨噬细胞吞噬活性、大鼠肝细胞糖原溶解和LDH释放进行比较。这些细胞毒性试验的敏感性差异很大,集落形成抑制试验对HL-60细胞的活力有相似的结果。“细胞毒性矩阵”原理是通过比较每种化学物质的细胞毒性而发展起来的。发现了细胞毒性基质的形态与化学结构之间的特征关系,表明细胞毒性基质可用于预测微污染物的来源和性质。©1994 by John Wiley & Sons, Inc.。
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