Nishiwaki-Matsushima R, Ohta T, Nishiwaki S, Suganuma M, Kohyama K, Ishikawa T, Carmichael W W, Fujiki H
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
J Cancer Res Clin Oncol. 1992;118(6):420-4. doi: 10.1007/BF01629424.
Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.
某些有毒蓝藻（蓝绿藻）水华对健康构成威胁，因为它们会产生有毒肽，即微囊藻毒素，可导致野生动物和家畜肝脏损伤。研究最广泛的微囊藻毒素是微囊藻毒素-LR，它是一种七肽，含有两种L-氨基酸，即亮氨酸和精氨酸。微囊藻毒素-LR对1型和2A型蛋白磷酸酶活性的抑制作用与已知的蛋白磷酸酶抑制剂和肿瘤促进剂冈田酸相似。我们在本报告中表明，在低于急性毒性水平的情况下应用微囊藻毒素-LR，可剂量依赖性地增加经二乙基亚硝胺启动的大鼠肝脏中谷胱甘肽S-转移酶胎盘形式的阳性灶数量和面积百分比。该结果通过两项动物实验独立获得。这一观察结果表明，微囊藻毒素-LR是一种通过抑制1型和2A型蛋白磷酸酶活性介导的新型肝脏肿瘤促进剂。这进一步证明了冈田酸途径是小鼠皮肤、大鼠腺胃和大鼠肝脏等各种器官肿瘤促进的普遍机制。
