中国药物警戒 ›› 2020, Vol. 17 ›› Issue (12): 861-866.
DOI: 10.19803/j.1672-8629.2020.12.03

• 基础研究 • 上一篇    下一篇

通关散的遗传毒性研究

王会萍1,2, 王恩力1,2, 徐娇艳1,2, 姚景春1,2*   

  1. 1鲁南制药集团股份有限公司新药安评中心,山东 临沂 273400;
    2中药制药共性技术国家重点实验室,山东 临沂 273400
  • 收稿日期:2020-04-14 修回日期:2020-12-07 出版日期:2020-12-15 发布日期:2020-12-07
  • 通讯作者: *姚景春,男,硕士,研究员,新药临床前药理毒理学研究。E-mail:yaojingchun@lunan.cn
  • 作者简介:王会萍,女,硕士,工程师,新药临床前药理毒理学研究。
  • 基金资助:
    山东省重大科技创新工程项目(2018CXGC1304)

Genetic Toxicity of Tongguan san

WANG Huiping1,2, WANG Enli1,2, XU Jiaoyan1,2, YAO Jingchun1,2*   

  1. 1Center For Drug Safety Evaluation of Lunan Pharmaceutical Group Corporation,Linyi Shandong 273400,China;
    2State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Linyi Shandong 273400,China
  • Received:2020-04-14 Revised:2020-12-07 Online:2020-12-15 Published:2020-12-07

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摘要： 目的 评价通关散的遗传毒性,为临床用药提供安全性依据。方法 通过体外细菌回复突变(Ames)实验、体外中国仓鼠肺细胞(CHL细胞)染色体畸变实验、小鼠骨髓微核实验,进行通关散的遗传毒性研究。Ames实验设312.5、625.0、1 250.0、2 500.0、5 000.0μg/皿5个剂量;体外CHL细胞染色体畸变实验,设立125.0、250.0、500.0μg/mL 3个剂量,通关散与CHL细胞分别接触6 h和24 h;小鼠骨髓微核实验,设立1 250.0、2 500.0、5 000.0 mg/kg 3个剂量,连续给药7 d,每天1次。结果 Ames实验,在S9代谢和非代谢活化条件下,通关散在312.5~5 000.0μg/皿浓度范围内,对所测5种菌株回变菌落数均未出现剂量依赖性增加,结果为阴性;CHL细胞染色体畸变实验,在S9代谢和非代谢活化条件下,通关散各剂量组诱导CHL细胞染色体畸变率与溶剂对照组相比,差异无统计学意义(P>0.05),且无剂量-反应关系;小鼠骨髓微核实验,通关散各剂量组小鼠骨髓嗜多染红细胞数微核率与溶剂对照组相比,差异无统计学意义(P>0.05)。结论 在该研究实验条件下,通关散未见潜在的遗传毒性。

关键词: 通关散, 遗传毒性, 体外细菌回复突变实验, 中国仓鼠肺细胞染色体畸变实验, 微核实验

Abstract: Objective To evaluate the genotoxicity of Tongguan san and provide safety data for evaluation of its clinical medication.Methods The in vitro bacterial reverse mutation (Ames) test, in vitro Chinese hamster lung cell (CHL) chromosome aberration test, and the mouse bone marrow micronucleus test were conducted to study the genetic toxicity of Tongguan san. In Ames test, there were five dose groups respectively as follows: 312.5、625.0、1250.0, 2500.0 and 5000.0 μg/plate. In CHL chromosome aberration assay, the doses were 125.0、250.0 and 500.0 μg/mL respectively while the exposure time was 6 and 24 h respectively. In vivo micronucleus assay, there were three dose groups: 1250.0、2500.0 and 5000.0 mg/kg, for 7 days, once per day.Results In the Ames test, under S9 metabolism and non-metabolic activation, the numbers of five strains of revertant colonies did not show any dose-dependent increase when the Tongguan san concentration ranged from 312.5 to 5000.0μg/plate, and the result of Ames test was negative. In CHL chromosome aberration test, under S9 metabolism and non-metabolic activation, there was no significant difference in the chromosome aberration rate between the control group and dosing groups of Tongguan san (P >0.05), so there was no dose-response relationship. In the micronucleus test of mouse bone marrow cells, the micronuclei rates of mice bone marrow cells in each dosing group of Tongguan san were not significantly different from those of the solvent control (P>0.05).Conclusion Under this test condition, there is no potential genotoxicity in Tongguan san.

Key words: Tongguan san, genotoxicity, Ames test, CHL chromosome aberration assay, micronucleus assay

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