PRODUCTION OF HYDROXYL RADICAL BY TALLYSOMYCIN AND COPPER(II)
PRODUCTION OF HYDROXYL RADICAL BY TALLYSOMYCIN AND COPPER(II)
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DOI：
10.1016/0014-5793(79)81037-6
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发表时间：
1979-01-01
期刊：
影响因子：
3.5
通讯作者：
OBERLEY, LW
中科院分区：
文献类型：
--
作者：
BUETTNER, GR;OBERLEY, LW
塔利霉素是一种与博来霉素结构相关的抗肿瘤抗生素。塔利霉素的作用机制似乎与博来霉素相似。博莱霉素诱导纯化的分离DNA链断裂[1—5]。博莱霉素也被证明会导致细胞内DNA断裂[5,6]。铁(H)似乎与博来霉素的作用机制有关。博莱霉素的作用模型如下[11]。博莱霉素可以与DNA结合。然后铁(H)可以附着在博来霉素上形成三元配合物。这种复合物在氧气的存在下，可以产生一种降解DNA的物种。我们最近表明，博来霉素和铁(H)产生羟基自由基[7]。由于' OH的高反应性，这种自由基很可能是博来霉素毒性的原因。Tallysomycin是第三代博来霉素类似物，已被发现在Walker 256癌和P-388白血病肿瘤系统以及多种细菌和真菌中比博来霉素更有效[S]。在其他肿瘤系统中也观察到抗肿瘤活性。
Tallysomycin is an antitumor antibiotic that is structurally related to bleomycin. The mechanism of action of tallysomycin appears to be similar to that of bleomycin. Bleomycin induces strand scission of purified isolated DNA [l--5]. Bleomycin has also been shown to produce breakage of intracellular DNA [5, 6]. Iron (H) appears to be associated with the mechanism of action of bleomycin. The following model for the action of bleomycin has been proposed [11. Bleomycin can bind to DNA. Fe (H) can then attach to the bleomycin to form a ternary complex. This complex, in the presence of oxygen, can then produce a species which degrades DNA. We have recently shown that bleomycin and Fe (H) produces the hydroxyl radical [7]. Because of the high reactivity of ‘OH, it is likely that this radical is responsible for the toxicity of bleomycin.Tallysomycin, a third generation bleomycin analogue, has been found to be more potent than bleomycin in the Walker 256 carcinoma and the P-388 leukemia tumor systems [S], as well as in a variety of bacteria and fungi [9]. Antitumor activity has also been observed for other tumor systems [9].