Braithwaite A W, Eichner R D, Waring P, Müllbacher A
Mol Immunol. 1987 Jan;24(1):47-55. doi: 10.1016/0161-5890(87)90110-6.
Gliotoxin, a member of the class of secondary fungal metabolites characterized by the presence of an epipolythiodioxopiperazine ring, caused fragmentation of spleen cell DNA as observed by flow cytometry and gel electrophoresis. Gliotoxin was found to cause substantial double-stranded DNA breakage in spleen cells which was dose- and time-dependent. The ability of gliotoxin to cause DNA breakage was also found to be specific to cell type. DNA breakage occurred in all cell types in which gliotoxin inhibited proliferation and so provides a general explanation as to how gliotoxin prevents cell proliferation. Other results showed that gliotoxin bound to a similar extent to both sensitive and resistant cells, indicating that differential uptake is not a likely mechanism to explain cell type selectivity. The results are discussed in terms of a mechanism for gliotoxin action involving genomic DNA as the central target.
Gliotoxin是一类次级真菌代谢产物中的一员，其特征在于存在一个表聚硫代二氧哌嗪环。通过流式细胞术和凝胶电泳观察发现，Gliotoxin会导致脾细胞DNA片段化。研究发现Gliotoxin会在脾细胞中引起大量双链DNA断裂，且具有剂量和时间依赖性。还发现Gliotoxin导致DNA断裂的能力具有细胞类型特异性。在Gliotoxin抑制增殖的所有细胞类型中都会发生DNA断裂，因此这为Gliotoxin如何阻止细胞增殖提供了一个一般性解释。其他结果表明，Gliotoxin与敏感细胞和耐药细胞的结合程度相似，这表明差异摄取不太可能是解释细胞类型选择性的机制。本文根据以基因组DNA为核心靶点的Gliotoxin作用机制对这些结果进行了讨论。
