Rao P V, Bhattacharya R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Toxicology. 1996 Nov 15;114(1):29-36. doi: 10.1016/s0300-483x(96)03413-0.
Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. Hepatotoxic and other toxic manifestations of MCLR are well documented. However, information on genotoxicity of MCLR is limited. The present investigation addresses the DNA damage induced by MCLR in mouse liver in vivo. The DNA strand breaks were measured by the fluorimetric analysis of DNA unwinding (FADU). MCLR at 0.5, 1.0 and 2.0 LD50 doses exhibited a dose and time-dependent DNA damage accompanied by similar effects on various enzymes of hepatic origin, e.g. lactate dehydrogenase, alkaline phosphatase and gamma glutamyl transferase. MCLR-induced genomic DNA fragmentation was also assessed qualitatively by agarose gel electrophoresis. MCLR induced random DNA fragmentation and DNA degradation. Glutathione (GSH) pretreatment significantly extended the survival time of animals exposed to 1.0 LD50 MCLR but offered only partial protection with regard to DNA damage. The DNA damage observed in the present study can be ascribed to activation of endonucleases.
微囊藻毒素-LR（MCLR）是由铜绿微囊藻产生的一种强效环状七肽肝毒素。MCLR的肝毒性和其他毒性表现已有充分记录。然而，关于MCLR遗传毒性的信息有限。本研究探讨了MCLR在小鼠肝脏中诱导的体内DNA损伤。通过DNA解旋荧光分析（FADU）测量DNA链断裂。0.5、1.0和2.0 LD50剂量的MCLR表现出剂量和时间依赖性的DNA损伤，并对各种肝脏来源的酶，如乳酸脱氢酶、碱性磷酸酶和γ-谷氨酰转移酶产生类似影响。还通过琼脂糖凝胶电泳对MCLR诱导的基因组DNA片段化进行了定性评估。MCLR诱导随机DNA片段化和DNA降解。谷胱甘肽（GSH）预处理显著延长了暴露于1.0 LD50 MCLR的动物的存活时间，但在DNA损伤方面仅提供了部分保护。本研究中观察到的DNA损伤可归因于核酸内切酶的激活。
