癌变·畸变·突变 ›› 2024, Vol. 36 ›› Issue (6): 491-496.doi: 10.3969/j.issn.1004-616x.2024.06.011

• 检测研究 • 上一篇    

精制鱼油的致畸致突变性检测

赵易敏1, 张娟娟1, 刘学武2, 张红贞2, 张维萍2, 章泽恒3   

  1. 1. 湖南普瑞玛药物研究中心有限公司, 湖南长沙 410329;
    2. 山东新华制药股份有限公司, 山东 淄博 255086;
    3. 湖南省药品审评与不良反应监测中心, 湖南 长沙 410013
  • 收稿日期:2023-09-20 修回日期:2024-03-12 发布日期:2024-12-04
  • 通讯作者: 章泽恒
  • 作者简介:赵易敏,E-mail:zhaoyimin@hnse.org.com。
  • 基金资助:
    长沙市“小荷”青年人才创新项目(2022年)

Teratogenicity and mutagenicity evaluation of refined fish oil

ZHAO Yimin1, ZHANG Juanjuan1, LIU Xuewu2, ZHANG Hongzhen2, ZHANG Weiping2, ZHANG Zeheng3   

  1. 1. Hunan Prima Pharmaceutical Research Center Co., Ltd., Changsha 410329, Hunan;
    2. Shandong Xinhua Pharmaceutical Company Limited, Zibo 255086, Shandong;
    3. Hunan Provincial Center for Drug Evaluation and Adverse Reaction Monitoring Center, Changsha 410013, Hunan, China
  • Received:2023-09-20 Revised:2024-03-12 Published:2024-12-04

摘要: 目的: 评价精制鱼油(DHA含量89.97%,EPA含量1.12%)是否具有致畸变和致突变作用。方法: 在SD雌性大鼠妊娠期第6~15天经口灌胃分别给予不同剂量(1.2、2.3、4.6 g/kg)精制鱼油,通过检测孕鼠体质量、妊娠结局、胎仔内脏和骨骼以及胎仔的生长发育等指标,评价精制鱼油的致畸作用。检测精制鱼油在活化与非活化条件下对鼠伤寒沙门氏菌TA97a、TA98、TA100、TA102、TA1535回变菌落数及菌落形态的影响;通过检测精制鱼油对正常ICR小鼠骨髓细胞微核率,精原细胞染色体畸变率、畸变细胞率的影响,评价其致突变作用。结果: 在致畸试验中,精制鱼油对孕鼠未观察到有害作用剂量(NOAEL)为4.6 g/kg;精制鱼油各剂量组(8~5 000 μg/皿)在代谢活化与非代谢活化条件下Ames试验均为阴性;精制鱼油各剂量组的小鼠骨髓细胞微核率,精原细胞染色体畸变率及畸变细胞率与对照组比较差异均无统计学意义(P>0.05),未见明显致突变作用。结论: 在本实验条件下,精制鱼油未见致畸和致突变作用。

关键词: 精制鱼油, 致畸性, 细菌回复突变, 微核, 染色体畸变, 遗传毒性

Abstract: OBJECTIVE: To evaluation of teratogenicity and mutagenicity of refined fish oil (DHA content 89.97%,EPA content 1.12%). METHODS: SD female rats were given different doses(1.2,2.3,4.6 g/kg) of refined fish oil by oral administration on the 6th to 15th day of pregnancy. The body weight,pregnancy outcome,fetal viscera and bone,and fetal growth and development of pregnant rats were measured to evaluate the teratogenic effect of the fish oil. Effects of refined fish oil on the colony number and colony morphology of Salmonella typhimurium TA97a,TA98,TA100,TA102 and TA1535 were detected under activated and non-activated conditions. Its mutagenicity was evaluated by detecting the micronucleus rate in bone marrow cells and chromosome aberration rate in spermatogonia from normal ICR mice. RESULTS: In the teratogenic test,the NOAEL of refined fish oil on pregnant mice was 4.6 g/kg. The Ames test results for all dose groups (8-5 000 μg/dish) was negative under both metabolic and non-metabolic activation conditions. Compared with the control group,the micronucleus rate,chromosome aberration rate and aberration rate in bone marrow cells for each dose group were insignificant (P>0.05),and there was no obvious mutagenicity. CONCLUSION: Under the experimental conditions,no teratogenic and mutagenic effects were observed in refined fish oil.

Key words: refined fish oil, teratogenicity, bacterial reverse mutation, micronucleus, chromosome aberration, genotoxicity

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