Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474002, India.
Environ Toxicol Pharmacol. 1998 Jan;5(1):1-6. doi: 10.1016/s1382-6689(97)00022-7.
Microcystins are a family of potent hepatotoxins and liver tumor promoters produced by several genera of cyanobacteria including Microcystis, Nodularia, Anabena, Nostoc, etc. They are chemically very stable and represent a public health threat when they occur in water used for human consumption. We investigated the DNA damage effects of M. aeruginosa UTEX 2385 in mouse liver in vivo and also in mammalian cells in vitro. The DNA damage effect is compared with purified toxin microcystin-LR (MCLR) in non-hepatic cells viz. baby hamster kidney cells (BHK-21) and mouse embryo fibroblasts primary cells (MEF). Cell-free extracts of UTEX 2385 induced significant DNA fragmentation at 0.5, 1 and 2 LD(50) (32.7, 65.4 and 130.8 mg/kg, respectively) and it was also time dependent. M. aeruginosa UTEX 2385 and MCLR induced significant DNA fragmentation in BHK-21 and MEF cells at 100 and 1.0 μg/ml concentration. Electrophoretic analysis revealed necrotic DNA damage by UTEX 2385 in vivo. Both the toxins caused smear in agarose gel electrophoresis indicating the necrotic DNA damage in MEF cells, whereas, multiple DNA fragments in BHK-21 cells. The DNA damage effect of the toxin is supported by data on hepatotoxicity in vivo and cytotoxicity in vitro.
微囊藻毒素是一类由蓝藻属的微囊藻、节旋藻、鱼腥藻、念珠藻等产生的强效肝毒素和肝肿瘤促进剂。它们在化学上非常稳定,当它们存在于供人类饮用的水中时,会对公共健康构成威胁。我们研究了铜绿微囊藻 UTEX 2385 在体内诱导小鼠肝损伤和体外诱导哺乳动物细胞损伤的 DNA 损伤效应。并将该损伤效应与非肝源性细胞(如仓鼠肾细胞(BHK-21)和小鼠胚胎成纤维细胞原代细胞(MEF))中的纯化毒素微囊藻毒素-LR(MCLR)进行了比较。UTEX 2385 的无细胞提取物在 0.5、1 和 2LD(50)(分别为 32.7、65.4 和 130.8mg/kg)时诱导明显的 DNA 片段化,且呈时间依赖性。铜绿微囊藻 UTEX 2385 和 MCLR 在 BHK-21 和 MEF 细胞中在 100 和 1.0μg/ml 浓度时也诱导明显的 DNA 片段化。电泳分析显示 UTEX 2385 在体内引起了坏死性 DNA 损伤。两种毒素在 MEF 细胞中均引起琼脂糖凝胶电泳中的弥散,表明存在坏死性 DNA 损伤,而在 BHK-21 细胞中则出现多个 DNA 片段。毒素的 DNA 损伤效应得到了体内肝毒性和体外细胞毒性数据的支持。