DNA damage induced by bleomycin in the presence of dibucaine is not predictive of cell growth inhibition.
DNA damage induced by bleomycin in the presence of dibucaine is not predictive of cell growth inhibition.
复制标题
在地布卡因存在的情况下，博来霉素诱导的 DNA 损伤不能预测细胞生长抑制。
DOI：
10.1021/bi00334a021
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发表时间：
1985
期刊：
影响因子：
2.9
通讯作者：
Sidney M. Hecht
中科院分区：
文献类型：
--
作者：
David E. Berry;R. Kilkuskie;Sidney M. Hecht
博来霉素的生长抑制和细胞杀伤被认为与这种抗生素切割染色体DNA的能力有关。由于博来霉素具有细胞内作用位点，因此其穿过生物膜的能力对于其作为抗肿瘤剂的总体有效性至关重要。局部麻醉剂地布卡因可增强膜流动性;因此，研究了该局部麻醉剂调节博来霉素对KB细胞作用的报告能力。在存在或不存在地布卡因的情况下，用各种博来霉素同类物处理细胞24小时。地布卡因增强了博来霉素A2、去甲基博来霉素A2、博来霉素B2和异博来霉素A2介导的细胞生长抑制。N-乙酰博莱霉素A2在不存在地布卡因的情况下不抑制细胞生长，但在存在地布卡因的情况下具有抑制作用。同时处理的细胞碱性蔗糖梯度上的DNA断裂分析显示，断裂也增强了存在下的地布卡因。增强程度因剂量和博来霉素同类物而异。N-乙酰博来霉素A2在不存在或存在地布卡因的情况下均不诱导DNA断裂。虽然生长抑制和净DNA断裂相关性相当好，在不存在地布卡因的情况下，每一个测试的博来霉素类似物，比例损失在地布卡因的存在下，和非常少的DNA断裂时，生长抑制是完全的。这些观察结果意味着，至少在地布卡因存在下，博来霉素可以介导除染色体DNA之外的某些位点的生长抑制，并且，给定净量的博来霉素类似物诱导的DNA损伤本身不产生特定程度的生长抑制。
Growth inhibition and cell killing by bleomycin are believed to be related to the ability of this antibiotic to cleave chromosomal DNA. Because bleomycin has an intracellular site of action, its ability to cross biological membranes must be critical to its overall effectiveness as an antitumor agent. The local anesthetic dibucaine acts to enhance membrane fluidity; therefore, the reported ability of this local anesthetic to modulate bleomycin effects on KB cells was investigated. Cells were treated with various bleomycin congeners in the presence or absence of dibucaine for 24 h. Dibucaine enhanced the inhibition of cell growth mediated by bleomycin A2, demethylbleomycin A2, bleomycin B2, and isobleomycin A2. N-Acetylbleomycin A2 did not inhibit cell growth in the absence of dibucaine, but it was inhibitory in the presence of dibucaine. Cells treated simultaneously for analysis of DNA breakage on alkaline sucrose gradients revealed that breakage was also enhanced in the presence of dibucaine. The degree of enhancement varied with dose and bleomycin congener. N-Acetylbleomycin A2 did not induce DNA breakage in either the absence or the presence of dibucaine. While growth inhibition and net DNA breakage correlated reasonably well in the absence of dibucaine for each bleomycin analogue tested, proportionality was lost in the presence of dibucaine, and very little DNA breakage was present when growth inhibition was complete. These observations imply that, at least in the presence of dibucaine, bleomycin may mediate growth inhibition at some locus in addition to chromosomal DNA and, also, that a given net amount of bleomycin analogue induced DNA damage per se does not produce a specific degree of growth inhibition.
DOI：
10.1016/s0021-9258(19)70209-9
发表时间：
1980-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Burger;Allen R. Berkowitz;J. Peisach;Susan Band
通讯作者：
R. Burger;Allen R. Berkowitz;J. Peisach;Susan Band
通过核基因型、生长期和金属离子控制体内（细胞）腐草霉素敏感性。
影响因子：
11.2
作者：
Moore,CW
通讯作者：
Moore,CW
他利霉素和博来霉素类似物对 PM-2 DNA 的 DNA 损伤以及单链和双链断裂活性的比较。
影响因子：
11.2
作者：
Mirabelli,CK;Huang,CH;Crooke,ST
通讯作者：
Crooke,ST