McDermott Catherine, Allshire Ashley, van Pelt Frank, Heffron James J A
Environmental Research Institute, University College Cork, Lee Maltings, Ireland
Toxicol Sci. 2008 Feb;101(2):263-74. doi: 10.1093/toxsci/kfm274. Epub 2007 Nov 2.
Humans are frequently exposed to mixtures of environmental pollutants at low levels over prolonged periods of time yet most toxicity studies deal with acute exposure to high concentrations of single chemicals. Investigation of the biological effects and possible toxic interactions during long-term exposure to such mixtures is warranted. Here Jurkat T-cells were exposed to toluene, n-hexane and methyl ethyl ketone in binary combination. Concentration ranges were centered on thresholds at which the individual agents caused cell toxicity under otherwise similar conditions, and concentrations were confirmed by headspace gas chromatography. After 5 days cells were harvested and toxicity measured in terms of membrane damage (lactate dehydrogenase [LDH] leakage), perturbations in Ca(2+) and changes in glutathione redox status. Data for all three endpoints were subjected to isobolographic analysis to test for interaction between components of the solvent mixture. Almost all combinations of toluene and n-hexane elicited greater than additive toxicity in terms of each of the three endpoints, as did methyl ethyl ketone (MEK)/n-hexane and MEK/toluene combinations for the LDH and glutathione endpoints. The main exceptions were the two combinations involving MEK, which caused less than additive effects on perturbations of Ca(2+). It is concluded that toxicity in immune-derived T cells may exhibit greater than additive effects when there is coexposure to organic solvents. This may have implications for risk assessment of environmental exposure to these agents.
人类经常在很长一段时间内低水平接触环境污染物混合物，但大多数毒性研究都涉及对高浓度单一化学物质的急性暴露。因此，有必要对长期接触此类混合物期间的生物效应和可能的毒性相互作用进行研究。在此，将人 Jurkat T 细胞暴露于甲苯、正己烷和甲乙酮的二元组合中。浓度范围以在其他条件相似的情况下各单一物质引起细胞毒性的阈值为中心，并通过顶空气相色谱法确认浓度。5 天后收获细胞，并根据膜损伤（乳酸脱氢酶 [LDH] 泄漏）、Ca(2+) 的扰动以及谷胱甘肽氧化还原状态的变化来测量毒性。对所有三个终点的数据进行等效线图分析，以测试溶剂混合物各成分之间的相互作用。就三个终点中的每一个而言，甲苯和正己烷的几乎所有组合都引发了大于相加毒性的效应，甲乙酮 (MEK)/正己烷和 MEK/甲苯组合在 LDH 和谷胱甘肽终点方面也是如此。主要例外是涉及 MEK 的两种组合，它们对 Ca(2+) 的扰动产生的效应小于相加效应。得出的结论是，当同时接触有机溶剂时，免疫来源的 T 细胞中的毒性可能表现出大于相加的效应。这可能对这些物质的环境暴露风险评估有影响。
