Keogh J P, Steffen B, Siegers C P
Institute for Toxicology, Medical University of Lübeck, Germany.
J Toxicol Environ Health. 1994 Nov;43(3):351-9. doi: 10.1080/15287399409531926.
Cytotoxicities of metal salts were determined in the intestinal epithelial cell line I-407 in microwell culture plates over 48 h using the widely utilized and accepted neutral red uptake procedure. Rank order cytotoxicities induced by the metal salts (in terms of LC50 values) were found to be HgCl2 (32 microM) > CdCl2 (53 microM) > CuCl2 (156 microM) > T12SO4 (377 microM) > Pb(NO3)2 (1.99 mM). Combined administration of the two most toxic metals at their LC50's showed that their toxicities were not additive or synergistic. The role of glutathione in determining toxicity induced by the metal salts in these cells was assessed by inhibition of its synthesis. Buthionine sulfoximine pretreatment at 1 mM, which was not toxic to the cells, caused sustained reduction in cellular glutathione content (to 13.8% after 48 h) and increased toxicities induced by HgCl2 (5.7-fold) and CuCl2 (1.44-fold) as shown by reductions in the LC50 values. Toxicity induced by the other metals remained unaffected. Administration of glutathione with either HgCl2 or CdCl2 did not protect the cells against their toxicity, and in the case of cadmium its toxicity was exacerbated. N-Acetylcysteine diminished toxicity induced by mercury but not cadmium.
采用广泛应用且被认可的中性红摄取法，在微孔培养板中对肠道上皮细胞系I-407进行了48小时的金属盐细胞毒性测定。发现金属盐诱导的细胞毒性排序（以半数致死浓度值计）为：HgCl2（32微摩尔）＞CdCl2（53微摩尔）＞CuCl2（156微摩尔）＞T12SO4（377微摩尔）＞Pb(NO3)2（1.99毫摩尔）。以半数致死浓度联合施用两种毒性最强的金属，结果表明它们的毒性并非相加或协同作用。通过抑制谷胱甘肽的合成来评估其在这些细胞中对金属盐诱导毒性的作用。1毫摩尔的丁硫氨酸亚砜胺预处理对细胞无毒，可导致细胞内谷胱甘肽含量持续降低（48小时后降至13.8%），并增加HgCl2（5.7倍）和CuCl2（1.44倍）诱导的毒性，表现为半数致死浓度值降低。其他金属诱导的毒性未受影响。同时施用谷胱甘肽与HgCl2或CdCl2并不能保护细胞免受其毒性影响，而且对于镉，其毒性反而加剧。N-乙酰半胱氨酸可降低汞诱导的毒性，但对镉无效。
