目的 使用毒性预测软件及细菌回复突变（Ames）试验评价茜素型蒽醌的基因突变风险。方法 通过毒性软件Toxtree、Derek Nexus和Sarah Nexus对茜素型蒽醌：茜草素、异茜草素、甲基异茜草素、甲基异茜草素-1-甲醚、茜素-1-甲醚、羟基茜草素、光泽汀进行致突变风险预测；每个受试物设置5个给药浓度，分别在有或无S9代谢活化条件下，使用5种鼠伤寒沙门氏菌TA97、TA100、TA102、TA1535和TA1537开展基于6孔板培养的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 软件基于蒽醌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，异茜草素和羟基茜草素可导致TA1537回复突变菌落数增加；光泽汀可诱导TA97、TA100和TA1537回复突变菌落数增加。在S9代谢活化下，异茜草素可导致TA97、TA100和TA1537回复突变菌落数增加；羟基茜草素可导致TA1537回复突变菌落数增加；光泽汀可导致TA97、TA100和TA1537回复突变菌落数增加；甲基异茜草素可导致TA97、TA100、TA102和TA1537回复突变菌落数大幅增加；甲基异茜草素-1-甲醚可导致TA100回复突变菌落数增加。结论 茜素型蒽醌受试物在有或无S9代谢条件下表现出不同程度、不同菌株的回复突变，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。

Objective Use genotoxicity prediction softwares and mini-Ames assay to evaluate the mutation risk of alizarin-type anthraquinones. Methods The mutation risk of a series of alizarin-type anthraquinones (alizarin, xanthopurpurin, rubiadin, rubiadin- 1-methyl ether, alizarin-1-methyl ether, prupurin, and lucidin) was predicted by toxicity prediction softwares (Toxtree, Derek Nexus and Sarah Nexus). The Ames test based on 6-well plate culture was carried out with five kinds of Salmonella typhimurium TA97, TA100, TA102, TA1535 and TA1537 with or without S9 metabolic activation to determine the effects of different substituents of the benzene ring on mutagenicity. Results Based on the presence of anthraquinone rings, the softwares predicted that all of these compounds had mutagenicity risk. Under the condition of non-S9 metabolic activation in the Ames assay, xanthopurpurin and purpurin could increase the number of mutant colonies of TA1537 compared with the control group. Lucidin could induce the increase of mutant colonies of TA97, TA100, and TA1537. Under the activation of S9 metabolism, xanthopurpurin could increase the number of reverse mutant colonies of TA97, TA100 and TA1537, and purpurin could increase the number of reverse mutant colonies of TA1537. Lucidin could increase the number of reverse mutation colonies of TA97, TA100, and TA1537. Rubiadin could cause TA97, TA100, TA102 and TA1537 reverse mutation colony numbers greatly increased, rubiadin-1-methyl ether can lead to TA100 reverse mutation colonies number increased. Conclusion Alizarin-type anthraquinones showed different degree of reverse mutationin different strains in the presence or absence of S9 metabolism. It is of great value to carry out further relevant studies to evaluate the toxicity risk for rational regulation of these compounds.

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国家自然科学基金资助项目（81503347、81503068）；国家十三五“重大新药创制”专项（2018ZX09201017-001）；中国食品药品检定研究院学科带头人培养基金（2019X4）