Cytotoxicity and DNA crosslinks produced by mitomycin analogs in aerobic and hypoxic EMT6 cells.
Cytotoxicity and DNA crosslinks produced by mitomycin analogs in aerobic and hypoxic EMT6 cells.
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DOI：
10.3727/095535491820873812
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发表时间：
1991
影响因子：
16.2
通讯作者：
S. Keyes;R. Loomis;M. DiGiovanna;C. Pritsos;S. Rockwell;A. Sartorelli
中科院分区：
文献类型：
--
作者：
S. Keyes;R. Loomis;M. DiGiovanna;C. Pritsos;S. Rockwell;A. Sartorelli
评估了几种丝裂霉素抗生素在氧合和缺氧条件下杀死 EMT6 肿瘤细胞和产生 DNA 交联的能力。所检查的药物包括丝裂霉素 C、卟啉霉素和丝裂霉素 C 的 7-氨甲基二硫缩醛衍生物 (BMY-43324)，所有这些药物对缺氧细胞的杀伤力均高于其含氧细胞；丝裂霉素 C 的 N,N'-二甲氨基亚甲基衍生物 (BMY-25282)，在含氧条件下比缺氧条件下的细胞毒性显着增强；以及卟啉霉素的 N,N'-二甲氨基亚甲基衍生物 (BL-6783)，其对缺氧和充氧细胞的毒性相同。通过碱性洗脱测量，所有这些试剂都会在 EMT6 细胞中产生 DNA 交联。无论使用丝裂霉素或氧合程度如何，产生给定量的细胞杀伤所需的交联数量相似，这表明 DNA 交联是丝裂霉素细胞破坏作用中的主要损伤。
Several mitomycin antibiotics were evaluated for their capacities to kill EMT6 tumor cells and to produce DNA crosslinks under conditions of oxygenation and hypoxia. The agents examined included mitomycin C, porfiromycin, and the 7-aminomethyl dithioacetal derivative of mitomycin C (BMY-43324), all of which caused greater kill of hypoxic cells than of their oxygenated counterparts; the N,N'-dimethylaminomethylene derivative of mitomycin C (BMY-25282), which was considerably more cytotoxic under oxygenated conditions than in hypoxia; and the N,N'-dimethylaminomethylene derivative of porfiromycin (BL-6783), which was equal in its toxicity to hypoxic and oxygenated cells. All of these agents produced DNA crosslinks in EMT6 cells, as measured by alkaline elution. The number of crosslinks required to produce a given amount of cell kill was similar, regardless of the mitomycin employed or the degree of oxygenation, suggesting that the crosslinking of DNA was a major lesion in the cytodestructive action of the mitomycins.