7种化合物细胞毒性与小鼠急性毒性的相关性研究

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (1): 42-45.

7种化合物细胞毒性与小鼠急性毒性的相关性研究

刘密凤, 彭双清, 盛治国, 解跃华, 董延生, 阳海鹰, 韩刚, 闫长会

中国人民解放军疾病预防控制所, 毒理学评价研究中心, 北京 100850

收稿日期:2007-09-15 修回日期:2007-12-25 出版日期:2008-01-26 发布日期:2020-10-13
通讯作者: 彭双清, 男, 研究员, 博士生导师, 主要从事药物安全性评价研究。Tel:010-66949631 E-mail:Pengsq@hotmail.com
作者简介:刘密凤, 女, 博士, 研究方向:药物安全性评价。Tel:010-52176669 　E-mail: hydgwxy@126.com
基金资助:
国家科技支撑计划“ 食品安全关键技术” 重大项目(2006BAK02A02)

Research on correlations between cytotoxicity and acute toxicity of seven compounds

LIU Mi-feng, PENG Shuang-qing, SHENG Zhi-guo, XIE Yue-hua, DONG Yan-sheng, YANG Haiying, HAN Gang, YAN Chang-hui

National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology,Beijing 100850, China

Received:2007-09-15 Revised:2007-12-25 Online:2008-01-26 Published:2020-10-13

摘要/Abstract

摘要： 目的为减少实验动物的使用, 利用化学物质的体外细胞毒性数据对体内急性毒性进行预测。方法 MTT 比色法检测7 种新化学实体对CHL 细胞的毒性作用, 利用RC(Registry of Cytotoxicity)预测模型对急性毒性LD50 值进行预测, 并使用小鼠急性毒性上下法进行验证。结果各化合物(1 ~ 7)细胞毒性IC50 值分别为0.43 、0.49 、0.18 、0.67 、3.03 、1.68 、1.79 mg/mL ;根据RC 预测模型, 急性毒性LD50 的预测值分别为2376.4 、2478.3 、1574.8 、2087.6 、4897.3 、3331.8 、3300.7 mg/kg。经上下法检测, 4 号化合物的LD50值为1634.0 mg/kg, 其余6 种化合物的LD50 值均大于2000.0 mg/kg。分别以预测值和实测值为依据对化合物毒性进行分级, 二者相比, 仅3 号和4号化合物毒性分级略有差异, 其它5 种化合物的毒性分级基本一致。结论体外细胞毒性数据可用来预测体内急性毒性, 减少实验动物使用。

关键词: 新化学实体, 急性毒性, 细胞毒性, RC 预测模型

Abstract: AIM: The study was undertaken to estimate acute toxicity in vivo using cytotoxicity data in vitro, in order to reduce animal usage in acute toxicity testing. METHODS: The basal cytotoxicity of seven compounds in Chinese hamster lung cell(CHL)cells were analyzed by MTT test, the LD50 values of acute toxicity were estimated by Registry of Cytotoxicity prediction model and validated by up-down method in mice. RESULTS: The IC50 values of compounds 1-7 in CHL cells were 0.43, 0.49, 0.18, 0.67, 3.03, 1.68 and 1.79 mg/mL, respectively. The predictive values of LD50 for compounds of 1-7 were 2376. 4, 2478. 3, 1574. 8, 2087.6, 4897.3, 3331.8 and 3300.7 mg/kg, respectively. The LD50 values for all compounds detected by up-down method were more than 2000.0 mg/kg except compound 4 with 1634. 0 mg/kg in female mice. Compared with the chemicals'toxicity classification based on predictive values and true values of LD50, the results indicated that toxicity classification of all compounds were basically at equal pace except compounds 3 and 4. CONCLUSION: The cytotoxicity data in vitro may be helpful in predicting acute toxicity in vivo and reducing the usage of laboratory animals.

Key words: new chemical entities, acute toxicity, cytotoxicity, RC prediction model

中图分类号:

R965.3

刘密凤, 彭双清, 盛治国, 解跃华, 董延生, 阳海鹰, 韩刚, 闫长会. 7种化合物细胞毒性与小鼠急性毒性的相关性研究[J]. 中国临床药理学与治疗学, 2008, 13(1): 42-45.

LIU Mi-feng, PENG Shuang-qing, SHENG Zhi-guo, XIE Yue-hua, DONG Yan-sheng, YANG Haiying, HAN Gang, YAN Chang-hui. Research on correlations between cytotoxicity and acute toxicity of seven compounds[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(1): 42-45.

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