RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia.
Toxins (Basel). 2021 Feb 2;13(2):107. doi: 10.3390/toxins13020107.
In the last decade, it has become evident that complex mixtures of cyanobacterial bioactive substances, simultaneously present in blooms, often exert adverse effects that are different from those of pure cyanotoxins, and awareness has been raised on the importance of studying complex mixtures and chemical interactions. We aimed to investigate cytotoxic and genotoxic effects of complex extracts from laboratory cultures of cyanobacterial species from different orders (, . ) and algae (), and examine possible relationships between the observed effects and toxin and retinoic acid (RA) content in the extracts. The cytotoxic and genotoxic effects of the extracts were studied in the human hepatocellular carcinoma HepG2 cell line, using the MTT assay, and the comet and cytokinesis-block micronucleus (cytome) assays, respectively. Liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) was used to detect toxins (microcystins (MC-LR, MC-RR, MC-YR) and cylindrospermopsin) and RAs (ATRA and 9cis-RA) in the extracts. Six out of eight extracts were cytotoxic (0.04-2 mg/mL), and five induced DNA strand breaks at non-cytotoxic concentrations (0.2-2 mg/mL). The extracts with genotoxic activity also had the highest content of RAs and there was a linear association between RA content and genotoxicity, indicating their possible involvement; however further research is needed to identify and confirm the compounds involved and to elucidate possible genotoxic effects of RAs.
在过去的十年中，人们已经明显认识到，蓝藻生物活性物质的复杂混合物同时存在于水华之中，通常会产生不同于纯藻毒素的不良影响，并且已经意识到研究复杂混合物和化学相互作用的重要性。我们旨在研究来自不同门（， ）和藻类（）的蓝藻物种的实验室培养物的复杂提取物的细胞毒性和遗传毒性作用，并检查观察到的作用与提取物中的毒素和视黄酸（RA）含量之间可能存在的关系。使用 MTT 测定法分别研究了提取物对人肝癌 HepG2 细胞系的细胞毒性和遗传毒性作用，并用彗星和胞质分裂阻滞微核（cytome）测定法研究了遗传毒性作用。使用液相色谱电喷雾电离质谱（LC/ESI-MS）检测了提取物中的毒素（微囊藻毒素（MC-LR、MC-RR、MC-YR）和柱孢藻毒素）和 RAs（ATRA 和 9cis-RA）。在八种提取物中有六种具有细胞毒性（0.04-2 mg/mL），并且有五种在非细胞毒性浓度（0.2-2 mg/mL）下诱导 DNA 链断裂。具有遗传毒性活性的提取物还具有最高含量的 RAs，并且 RA 含量与遗传毒性之间存在线性关联，表明它们可能参与其中；但是，需要进一步研究以鉴定和确认所涉及的化合物，并阐明 RAs 的可能遗传毒性作用。
