Aiub Claudia, Giannerini Ana, Ferreira Flavia, Mazzei José, Stankevicins Luiza, Lobo-Hajdu Gisele, Guimarães Pedro, Hajdu Eduardo, Felzenszwalb Israel
Department of Cellular Biology, Division of Genetics, Salzburg University, Salzburg A5020, Austria.
Mutat Res. 2006 Dec 10;611(1-2):34-41. doi: 10.1016/j.mrgentox.2006.06.035. Epub 2006 Sep 20.
A range of biologically active secondary metabolites with pharmacological application has been reported to occur in marine sponges. The present study was undertaken to provide a set of data on the safety of a hydro-alcoholic extract (ALE) and an aqueous fraction (AQE) from Aplysina fulva Pallas, 1766 (Aplysinidae, Verongida, Porifera). Salmonella typhimurium strains TA97, TA98, TA100 and TA102, Escherichia coli strains PQ65, OG40, OG100, PQ35 and PQ37 and Balb/c 3T3 mouse fibroblasts were used to detect induction of DNA lesions by ALE and AQE. Assays used for these analyses were a bacterial (reverse) mutation assay (Ames test), the SOS-chromotest and the comet assay. Both extracts presented identical infrared 2-oxazolidone spectra. ALE treatment induced a higher frequency of type-4 comets, indicative of increasing DNA migration, in the alkaline comet assay. ALE also induced a weak genotoxic effect, as expressed by the induction factor (IF) values in the test with E. coli strain PQ35 (IF=1.5) and by cytotoxic effects in strains PQ35, PQ65 and PQ37. Positive SOS induction (IF=1.7) was detected in strain PQ37 treated with diluted AQE. No genotoxic effects were observed in strains PQ35, PQ65, OG40 and OG 100 after treatment with AQE dilutions. Using the bacterial (reverse) mutation test and survival assays with or without S9 mix, after 60min of pre-incubation, we observed for strain TA97 treated with ALE a weak mutagenic response (MI=2.2), while cytotoxic effects were seen for strains TA98, TA100 and TA102. AQE did not show mutagenic activity in any of the strains tested, but a weak cytotoxic effect was noted in strain TA102. Our data suggest that both ALE and AQE from A. fulva induce DNA breaks leading to cytotoxicity and mutagenicity under the conditions used.
据报道，海洋海绵中存在一系列具有药理学应用价值的生物活性次生代谢产物。本研究旨在提供一组关于1766年帕拉斯棕黄海绵（Aplysinidae科，Verongida目，多孔动物门）的水醇提取物（ALE）和水相部分（AQE）安全性的数据。使用鼠伤寒沙门氏菌菌株TA97、TA98、TA100和TA102、大肠杆菌菌株PQ65、OG40、OG100、PQ35和PQ37以及Balb/c 3T3小鼠成纤维细胞来检测ALE和AQE对DNA损伤的诱导作用。用于这些分析的检测方法包括细菌（反向）突变检测（艾姆斯试验）、SOS-显色试验和彗星试验。两种提取物呈现相同的红外2-恶唑烷酮光谱。在碱性彗星试验中，ALE处理诱导出更高频率的4型彗星，这表明DNA迁移增加。ALE还诱导出微弱的遗传毒性效应，如在大肠杆菌菌株PQ35试验中的诱导因子（IF）值（IF = 1.5）以及在菌株PQ35、PQ65和PQ37中的细胞毒性效应所示。在用稀释的AQE处理的菌株PQ37中检测到阳性SOS诱导（IF = 1.7）。在用AQE稀释液处理后，在菌株PQ35、PQ65、OG40和OG100中未观察到遗传毒性效应。使用细菌（反向）突变试验以及在有或无S9混合物的情况下进行存活试验，预孵育60分钟后，我们观察到用ALE处理的菌株TA97有微弱的诱变反应（MI = 2.2），而在菌株TA98、TA100和TA102中观察到细胞毒性效应。AQE在任何测试菌株中均未显示诱变活性，但在菌株TA102中观察到微弱的细胞毒性效应。我们的数据表明，在所用条件下，来自棕黄海绵的ALE和AQE均诱导DNA断裂，导致细胞毒性和诱变性。
