[關鍵詞]
[摘要]
目的 使用毒性預測軟件及細菌回復突變(Ames)試驗評價茜素型蒽醌的基因突變風險。方法 通過毒性軟件Toxtree、Derek Nexus和Sarah Nexus對茜素型蒽醌:茜草素、異茜草素、甲基異茜草素、甲基異茜草素-1-甲醚、茜素-1-甲醚、羥基茜草素、光澤汀進行致突變風險預測;每個受試物設置5個給藥濃度,分別在有或無S9代謝活化條件下,使用5種鼠傷寒沙門氏菌TA97、TA100、TA102、TA1535和TA1537開展基于6孔板培養(yǎng)的Ames試驗,判斷該類化合物苯環(huán)上不同取代基對致突變性的影響。結果 軟件基于蒽醌環(huán)的存在預測該類化合物均具有致突變風險。在非S9代謝活化下,異茜草素和羥基茜草素可導致TA1537回復突變菌落數(shù)增加;光澤汀可誘導TA97、TA100和TA1537回復突變菌落數(shù)增加。在S9代謝活化下,異茜草素可導致TA97、TA100和TA1537回復突變菌落數(shù)增加;羥基茜草素可導致TA1537回復突變菌落數(shù)增加;光澤汀可導致TA97、TA100和TA1537回復突變菌落數(shù)增加;甲基異茜草素可導致TA97、TA100、TA102和TA1537回復突變菌落數(shù)大幅增加;甲基異茜草素-1-甲醚可導致TA100回復突變菌落數(shù)增加。結論 茜素型蒽醌受試物在有或無S9代謝條件下表現(xiàn)出不同程度、不同菌株的回復突變,開展相關研究評價其毒性風險對該類化合物合理監(jiān)管具有重要價值。
[Key word]
[Abstract]
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.
[中圖分類號]
R994
[基金項目]
國家自然科學基金資助項目(81503347、81503068);國家十三五“重大新藥創(chuàng)制”專項(2018ZX09201017-001);中國食品藥品檢定研究院學科帶頭人培養(yǎng)基金(2019X4)