苯酚类化合物基因突变风险评价研究

doi:10.19803/j.1672-8629.2022.08.11

中国药物警戒 ›› 2022, Vol. 19 ›› Issue (8): 868-872.
DOI: 10.19803/j.1672-8629.2022.08.11

苯酚类化合物基因突变风险评价研究

文海若¹, 叶倩^1,2Δ, 杨颖^1,2, 宋捷¹, 汪祺^3*, 王雪^1#

¹中国食品药品检定研究院国家药物安全评价监测中心,药物非临床安全性评价研究北京市重点实验室,北京 100176;
²中国药科大学,江苏南京 211198;
³中国食品药品检定研究院中药民族药检定所,北京 100050

收稿日期:2021-06-09 出版日期:2022-08-15 发布日期:2022-08-15
通讯作者: ^*汪祺,女,博士,研究员,药理毒理。E-mail：sansan8251@sina.com;^#为共同通信作者。
作者简介:文海若,女,博士,研究员,遗传毒理。^Δ为并列第一作者。
基金资助:
国家自然科学基金资助项目(81503347, 81503068); 中国食品药品检定研究院学科带头人培养基金（2019X4）

Gene mutation risk assessment of phenolic compounds

WEN Hairuo¹, YE Qian^1,2Δ, YANG Ying^1,2, SONG Jie¹, WANG Qi^3*, WANG Xue^1#

¹National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing 100176, China;
²China Pharmaceutical University, Nanjing Jiangsu 211198, China;
³National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100050, China

Received:2021-06-09 Online:2022-08-15 Published:2022-08-15

摘要/Abstract

摘要： 目的使用毒性预测软件和细菌回复突变试验（Ames）评价苯酚类化合物的基因突变风险。方法通过毒性预测软件对一系列苯酚类化合物进行致突变风险预测,在不同剂量、有或无S9代谢条件下进行六孔板Ames试验,判断该类化合物苯环上不同取代基对致突变性的影响。结果软件基于羟基苯环的存在预测该类化合物均具有致突变风险。在非S9代谢活化下,对氯苯乙酰胺可导致TA98回复突变菌落数增加,对硝基氯苯则导致TA100和TA102回复突变菌落数增加。在S9代谢活化下,对硝基氯苯导致TA100和TA1535回复突变菌落数增加,增加倍数高于无代谢活化条件,且存在浓度效应相关性。结论对氯苯乙酰胺和对硝基氯苯存在致细菌突变性,对硝基氯苯的致突变性在代谢活化后有所增加。开展相关研究评价其毒性风险对该类化合物合理监管具有重要价值。

关键词: 苯酚, 对乙酰氨基酚, 基因突变, 遗传毒性, 构效预测, 六孔板突变试验

Abstract: Objective To evaluate the mutation risk of phenolic compounds using toxicity prediction software and bacterial reverse mutation test (Ames test). Methods The mutagenic risk of a series of phenolic compounds was predicted by toxicity software, and the six-well plate Ames test was performed at different doses, and with or without S9 metabolism, to determine the effects of different substituents on the benzene ring of these compounds on their mutagenicities. Results It was predicted by software that these compounds were all mutagenic based on the presence of hydroxybenzene rings. Under non-S9 metabolic activation, p-chlorophenylacetamide led to an increase in the number of the revertants of TA98, while p-nitrochlorobenzene increased the number of the revertants of TA100 and TA102. Under the metabolic activation of S9, p-nitrochlorobenzene led to an increase in the number of the revertants of TA100 and TA1535, and the increase was far more significant than that without metabolic activation, so there was a concentration effect correlation. Conclusion There are bacterial mutagenicities of p-chlorophenylacetamide and p-nitrochlorobenzene, and the mutagenicity of p-nitrochlorobenzene increases after metabolic activation. It is of great value to carry out related research to evaluate its toxicity risk for rational regulation of such compounds.

Key words: phenol, N-acetyl-p-aminophenol, gene mutation, genotoxicity, structure-activity prediction, six-well plate Ames test

中图分类号:

文海若, 叶倩, 杨颖, 宋捷, 汪祺, 王雪. 苯酚类化合物基因突变风险评价研究[J]. 中国药物警戒, 2022, 19(8): 868-872.

WEN Hairuo, YE Qian, YANG Ying, SONG Jie, WANG Qi, WANG Xue. Gene mutation risk assessment of phenolic compounds[J]. Chinese Journal of Pharmacovigilance, 2022, 19(8): 868-872.

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苯酚类化合物基因突变风险评价研究

Gene mutation risk assessment of phenolic compounds

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