几种3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚的DNA亲和力与致突变性之间存在关联。
There is a correlation between the DNA affinity and mutagenicity of several 3-amino-1-methyl-5H-pyrido[4,3-b]indoles.
作者信息
Pezzuto J M, Lau P P, Luh Y, Moore P D, Wogan G N, Hecht S M
出版信息
Proc Natl Acad Sci U S A. 1980 Mar;77(3):1427-31. doi: 10.1073/pnas.77.3.1427.
Abstract
3-Amino-1-methyl-5H-pyrido[4,3-b]indole, previously reported to be a component of tryptophan pyrolysates, is an intensely mutagenic compound requiring microsomal activation for expression of mutagenicity. We have found that this species and several synthetic analogs interact noncovalently with calf thymus DNA, as judged by both fluorescence quenching and differential dialysis. Remarkably, this noncovalent interaction correlated with the mutagenic potential of the compounds in a bacterial mutagenesis assay. Therefore, it is suggested that the mechanism of mutagenesis involves metabolic activation followed by physicochemical interaction with DNA; for these compounds, the latter step may be limiting for the expression of mutagenicity.
摘要
3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚，先前报道为色氨酸热解产物的一种成分，是一种极强的诱变化合物，需要微粒体激活才能表现出诱变性。我们发现，通过荧光猝灭和差示透析判断，该物质及其几种合成类似物与小牛胸腺DNA发生非共价相互作用。值得注意的是，这种非共价相互作用与细菌诱变试验中化合物的诱变潜力相关。因此，有人提出诱变机制包括代谢激活，随后与DNA发生物理化学相互作用；对于这些化合物，后一步骤可能是诱变性表达的限制因素。
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