MULTIPLE EFFECTS OF 3-AMINOBENZAMIDE ON DNA DAMAGE INDUCED BY CISPLATIN (DDP) IN DDP-SENSITIVE AND DDP-RESISTANT RAT OVARIAN TUMOR-CELL LINES
MULTIPLE EFFECTS OF 3-AMINOBENZAMIDE ON DNA DAMAGE INDUCED BY CISPLATIN (DDP) IN DDP-SENSITIVE AND DDP-RESISTANT RAT OVARIAN TUMOR-CELL LINES
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DOI：
10.1016/0304-3835(92)90005-g
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发表时间：
1992-10-30
期刊：
影响因子：
9.7
通讯作者：
ZELLER, WJ
中科院分区：
文献类型：
--
作者：
CHEN, G;ZELLER, WJ
为探讨3-氨基苯甲酰胺（3AB）逆转大鼠卵巢癌细胞系顺铂（DDP）耐药的机制，采用动力学方法研究了3AB对DDP诱导的DNA损伤和修复的影响。DDP耐药（0-342/DDP）和敏感（0-342）的大鼠卵巢癌细胞在DDP暴露后12 h和24 h分别发生DNA单链断裂（SSB）。在O-342/DDP细胞中，3AB在24 h（P < 0.02）和48 h（P < 0.01）均能显著增加SSB的形成。在较小程度上（P > 0. 05），0-342细胞中也观察到类似的趋势。在0-342或0-342/DDP细胞中，DDP形成的DNA链间交联（ISCL）在12 h时达到最大值，但在耐药细胞中，它们都要低得多，并且更快地被去除。3AB在敏感细胞中作用12 h后即降低ISCL，24 h达最大值（P < 0.05），而在耐药细胞中作用12 h后降低ISCL，24 h无影响，48 h后升高ISCL。因此，3AB对DDP诱导的DNA损伤和修复具有多重作用，3AB对0-342/DDP细胞48 h DNA-ISCL的增加可能与其化疗增敏作用有关。
To investigate the mechanisms by which 3-aminobenzamide (3AB) reverses cisplatin (DDP) resistance in a rat ovarian tumor cell line, the effects of 3AB on DDP-induced DNA damage and repair were kinetically determined over a post-exposure period of 48 h. DNA single strand breaks (SSB) occurred maximally 12 h and 24 h following DDP exposure in DDP-resistant (0-342/DDP) and -sensitive (0-342) rat ovarian tumor cells, respectively. 3AB, present during and after the exposure, significantly increased SSB formation by DDP at 24 h (P < 0.02) and 48 h (P < 0.01) in O-342/DDP cells. To a lesser extent (P > 0. 05), a similar tendency was also observed in 0-342 cells. Formation of DNA interstrand cross-links (ISCL) by DDP reached a maximum by 12 h in either 0-342 or 0-342/DDP cells, but in the resistant cells they were both much lower and more rapidly removed. 3AB decreased ISCL in the sensitive cells at 12 h and thereafter with a maximum at 24 h (P < 0.05), while in the resistant cells the same treatment decreased ISCL at 12 h, had no effect at 24 h and increased ISCL at 48 h following DDP treatment. Therefore, it is concluded that 3AB has multiple effects on DNA damage and repair induced by DDP in both cell lines and increase of DNA-ISCL by 3AB at 48 h after the exposure in 0-342/DDP cells might be related to its chemosensitizing effect in this line.