6,7-dimethoxycoumarin attenuated cisplatin-induced DNA interstrand crosslink and DNA-protein crosslink in primary cultured rabbit kidney proximal tubular cells.

Zhongguo yao li xue bao = Acta pharmacologica Sinica Pub Date : 1999-05-01

S J Liu, S W Zhou

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Abstract

Aim: To study the mechanism of cisplatin interaction with DNA, and the attenuating effects of 6,7-dimethoxycoumarin (DMOC) on crosslink.

Methods: Primary cultured rabbit kidney proximal tubular cells (PTC) were established. DNA interstrand crosslink was assayed with ethidium bromide binding and DNA-protein crosslink with 125I-postlabelling. PTC were incubated with cisplatin for 24 h. DMOC was preincubated with PTC for 24 h, and cisplatin (26 mumol.L-1) was added into culture and incubated for another 24 h.

Results: Cisplatin induced formation of DNA interstrand crosslink (13, 26, 52, and 78 mumol.L-1) and DNA-protein crosslink (26, 52, and 78 mumol.L-1) (P < 0.01). DNA interstrand crosslink in DMOC (0.4, 4, and 8 mg.L-1) and DNA-protein crosslink in DMOC (4, 8 mg.L-1) were less than those in cisplatin group (26 mumol.L-1), respectively (P < 0.01).

Conclusion: The mechanisms of cisplatin interaction with DNA in PTC were DNA interstrand crosslink and DNA-protein crosslink, and DMOC attenuated these effects in vitro.

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6,7-二甲氧基香豆素减弱顺铂诱导的兔肾近端小管细胞DNA链间交联和DNA-蛋白交联。

目的:研究顺铂与DNA相互作用的机制，以及6,7-二甲氧基香豆素(DMOC)对交联的减弱作用。方法:建立原代培养兔肾近端小管细胞(PTC)。采用溴化乙啶结合法测定DNA链间交联，采用125i后标记法测定DNA-蛋白交联。PTC与顺铂共孵育24 h, DMOC与PTC共预孵育24 h，加入顺铂(26、26、52、78 mumol.L-1)再孵育24 h。结果:顺铂诱导DNA链间交联(13、26、52、78 mumol.L-1)和DNA-蛋白交联(26、52、78 mumol.L-1)的形成(P < 0.01)。DMOC组(0.4、4、8 mg.L-1) DNA链间交联和DMOC组(4、8 mg.L-1) DNA-蛋白交联均低于顺铂组(26 mmol . l -1) (P < 0.01)。结论:顺铂在PTC中与DNA的相互作用机制为DNA链间交联和DNA-蛋白交联，DMOC在体外可减弱这两种作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Zhongguo yao li xue bao = Acta pharmacologica Sinica

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