Van Pelt F N, Hassing I G, Stelling M A, Seinen W, Blaauboer B J
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Toxicol Appl Pharmacol. 1992 Apr;113(2):240-5. doi: 10.1016/0041-008x(92)90120-h.
Polychlorinated aromatic hydrocarbons modulate the proliferation and differentiation of human epidermal cells in vivo and in culture. One of the earliest events in the process of terminal differentiation is the increase in cell size. In this report the usefulness of morphometric cell size analysis as a quantifiable marker for chemical-induced differentiation was examined. Concentration-related increases in cell size distribution were induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 2,3,4,7,8-pentachlorodibenzofuran in normal human keratinocytes and cells from an SV40-transformed keratinocyte cell line (SVK14) whereas the analog 1,2,3,4-tetrachlorodibenzo-p-dioxin did not affect the cell size distribution up to a concentration of 100 nM. The minimal effective concentrations of five 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins/dibenzofurans and a coplanar polychlorbiphenyl necessary to induce an increase in cell size distribution were determined in SVK14 cells. It was found that the potency of these compounds relative to that of 2,3,7,8-TCDD correlated well with the toxicity equivalency factors observed in other test systems. This indicates that the keratinocyte cell assay is a useful method for establishing the relative potency of various "dioxins" and their mixtures.
多氯代芳烃在体内和体外培养中调节人表皮细胞的增殖和分化。终末分化过程中最早出现的事件之一是细胞大小增加。在本报告中，研究了形态计量细胞大小分析作为化学诱导分化的可量化标志物的实用性。在正常人角质形成细胞和来自SV40转化角质形成细胞系（SVK14）的细胞中，2,3,7,8-四氯二苯并 - 对 - 二恶英（2,3,7,8-TCDD）和2,3,4,7,8-五氯二苯并呋喃诱导细胞大小分布呈浓度相关增加，而类似物1,2,3,4-四氯二苯并 - 对 - 二恶英在浓度高达100 nM时不影响细胞大小分布。在SVK14细胞中确定了五种2,3,7,8-取代的多氯代二苯并 - 对 - 二恶英/二苯并呋喃和一种共平面多氯联苯诱导细胞大小分布增加所需的最低有效浓度。发现这些化合物相对于2,3,7,8-TCDD的效力与在其他测试系统中观察到的毒性当量因子密切相关。这表明角质形成细胞试验是确定各种“二恶英”及其混合物相对效力的有用方法。
