[關(guān)鍵詞]
[摘要]
目的 使用毒性預(yù)測(cè)軟件及細(xì)菌回復(fù)突變(Ames)試驗(yàn)評(píng)價(jià)茜素型蒽醌的基因突變風(fēng)險(xiǎn)。方法 通過毒性軟件Toxtree、Derek Nexus和Sarah Nexus對(duì)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(jìn)行致突變風(fēng)險(xiǎn)預(yù)測(cè);每個(gè)受試物設(shè)置5個(gè)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(yàn),判斷該類化合物苯環(huán)上不同取代基對(duì)致突變性的影響。結(jié)果 軟件基于蒽醌環(huán)的存在預(yù)測(cè)該類化合物均具有致突變風(fēng)險(xiǎn)。在非S9代謝活化下,異茜草素和羥基茜草素可導(dǎo)致TA1537回復(fù)突變菌落數(shù)增加;光澤汀可誘導(dǎo)TA97、TA100和TA1537回復(fù)突變菌落數(shù)增加。在S9代謝活化下,異茜草素可導(dǎo)致TA97、TA100和TA1537回復(fù)突變菌落數(shù)增加;羥基茜草素可導(dǎo)致TA1537回復(fù)突變菌落數(shù)增加;光澤汀可導(dǎo)致TA97、TA100和TA1537回復(fù)突變菌落數(shù)增加;甲基異茜草素可導(dǎo)致TA97、TA100、TA102和TA1537回復(fù)突變菌落數(shù)大幅增加;甲基異茜草素-1-甲醚可導(dǎo)致TA100回復(fù)突變菌落數(shù)增加。結(jié)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(fù)突變,開展相關(guān)研究評(píng)價(jià)其毒性風(fēng)險(xiǎn)對(duì)該類化合物合理監(jiān)管具有重要價(jià)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(hào)]
R994
[基金項(xiàng)目]
國家自然科學(xué)基金資助項(xiàng)目(81503347、81503068);國家十三五“重大新藥創(chuàng)制”專項(xiàng)(2018ZX09201017-001);中國食品藥品檢定研究院學(xué)科帶頭人培養(yǎng)基金(2019X4)