Correlation of chemical acute toxicity between the nematode and the rodent
Correlation of chemical acute toxicity between the nematode and the rodent
复制标题
线虫与啮齿动物化学急性毒性的相关性
DOI：
10.1039/c3tx50039j
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发表时间：
2013-01-01
影响因子：
2.1
通讯作者：
Li, Guojun
中科院分区：
文献类型：
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作者：
Li, Yu;Gao, Shan;Li, Guojun
任何非啮齿动物模型系统用于化学毒性筛选的效用取决于其响应与啮齿动物中毒性反应之间的相关性水平。对秀丽隐杆线虫（Caillushabditis elegans，C. elegans）可以快速和廉价;然而，很少有研究将线虫的毒性反应与啮齿动物急性毒性数据进行比较。采用C.优美的将线虫暴露于96孔板中不同浓度的化学物质中24小时。在2、4、12和24 h观察致死率，并通过Probit法计算半数致死浓度（LC 50）。另外，在10.000、21.500和46.400 mg ml−1浓度下，在1、8、16和20 h计数致死率，以获得半数致死时间（LT 50）。结果表明，化学pH值对C. elegans LC 50值。C. elegans大于2.75。除4种酸性物质外，C. 12 h和24 h的小鼠/大鼠LD_（50）均与Elegans呈显著正相关（r > 0.72，p < 0.01）。在C. elegans，C.线虫的LC_（50）与大鼠LD_（50）的相关性（r = 0.885）大于小鼠与大鼠LD_（50）的相关性（r = 0.879）;线虫对小鼠的LC_（50）和LD_（50）（r = 0.741）低于小鼠对大鼠的LD_（50）。进一步将数据与利用人表皮角质形成细胞（NHK）的体外细胞毒性模型进行比较。数据表明，C.线虫LC_（50）与大鼠LD_（50）的相关性与小鼠LD_（50）与大鼠LD_（50）的相关性相当（r = 0.879），强于NHK细胞IC_（50）与大鼠LD_（50）的相关性（r = 0.844）。此外，C.表明二者均可作为化学品急性毒性试验的毒性效应指标。综上所述，C.线虫可能是预测化学品对啮齿动物急性毒性的一个有价值的模型。
The utility of any non-rodent model system for chemical toxicity screening depends on the level of correlation between its responses and toxic reactions in rodents. Toxicity assays in the nematode Caenorhabditis elegans (C. elegans) can be fast and inexpensive; however few studies have been performed comparing toxic responses in the nematode with data on acute rodent toxicity. We assayed the acute toxicity of 21 types of chemicals in different toxicity categories using C. elegans. The nematodes were exposed to different concentrations of chemicals in 96-well plate for 24 h. The lethality rate was observed at 2, 4, 12 and 24 h, and median lethal concentration (LC50) was calculated by the Probit method. The lethality rate was counted at 1, 8, 16 and 20 h additionally at the concentrations of 10.000, 21.500 and 46.400 mg ml−1 to acquire median lethal times (LT50). The results indicated that the chemical pH could affect the C. elegans LC50 value. The pH toleration range for C. elegans was more than 2.75. Excluding 4 types of acidic chemicals, there were positive correlations between LC50s of C. elegans and LD50s of mouse/rat (r > 0.72, p < 0.01) after both 12 h and 24 h exposure. As to the LC50 data following a 24 h exposure in C. elegans, the correlation of C. elegans LC50s vs. rat LD50s (r = 0.885) was greater than the correlation of mouse vs. rat LD50s (r = 0.879), while the correlation of C. elegans LC50s vs. mouse LD50s (r = 0.741) was lower relative to that of mouse vs. rat LD50s. The data were further compared with an in vitro cytotoxicity model utilizing human epidermal keratinocytes (NHK). The data indicate that the correlation of C. elegans LC50s vs. rat LD50s was equal to the correlation of mouse vs. rat LD50s (r = 0.879), and was stronger than the correlation of NHK cell IC50s vs. rat LD50s (r = 0.844). In addition, LT50 was significantly correlative with the LC50 of C. elegans, indicating that both can be utilized as toxic effect index for further study on acute toxicity testing of chemicals. In summary, C. elegans may be a valuable model for predicting chemicals’ acute toxicity in rodents.