Effect of diethyldithiocarbamate rescue on tumor response to cis-platinum in a rat model.
Effect of diethyldithiocarbamate rescue on tumor response to cis-platinum in a rat model.
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DOI：
10.1073/pnas.77.9.5441
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发表时间：
1980-09
影响因子：
11.1
通讯作者：
R. Borch;J. Katz;P. Lieder;M. E. Pleasants
中科院分区：
文献类型：
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作者：
R. Borch;J. Katz;P. Lieder;M. E. Pleasants
给雌性F344大鼠腹腔注射或静脉注射二乙基二硫代氨基甲酸钠（DDTC）750 mg/kg，可有效抑制顺铂（NSC-119875）的肾毒性作用。给大鼠接种乳腺肿瘤13762，10天后给予DDP（2.0或8.0 mg/kg）治疗，并给予或不给予DDTC补救（腹腔注射750 mg/kg或静脉注射100 mg/kg）。在所有实验中，在有或没有补救的情况下，肿瘤大小的初始减小是相同的。然而，高剂量腹腔内救援，导致更早的复发和更快的进展，在两个DDP剂量比观察到的救援的情况下。低剂量静脉内补救治疗导致的肿瘤反应与未进行补救治疗时观察到的反应相同。尿中游离DDTC的排泄量增加，通过预先管理的乙酰唑胺，但是，这种组合是更有毒的DDP给药后，大鼠比DDTC单独。DDTC静脉给药似乎是将该配体递送至肾脏的最有效途径。这些结果支持了我们早期的机制假设，并证明了DDTC抑制顺铂毒性而不抑制抗肿瘤作用的可行性。
The nephrotoxic effects of cis-dichlorodiamineplatinum(II) (NSC-119875) (DDP) in female F344 rats were effectively inhibited by administration of sodium diethyldithiocarbamate (DDTC) in doses of 750 mg/kg intraperitoneally or 100 mg/kg intravenously 2 hr after administration of DDP. Rats were inoculated with mammary tumor 13762 and treated after 10 days with DDP (2.0 or 8.0 mg/kg) with or without DDTC rescue (750 mg/kg intraperitoneally or 100 mg/kg intravenously). Initial reductions in tumor size were identical with or without rescue in all experiments. High-dose intraperitoneal rescue, however, resulted in earlier relapse and more rapid progressions at both DDP doses than was observed in the absence of rescue. Low-dose intravenous rescue led to a tumor response identical to that observed without rescue. Urinary excretion of free DDTC was increased by prior administration of acetazolamide; however, this combination was more toxic to rats after DDP administration than was DDTC alone. Intravenous administration of DDTC appeared to be the most effective route for delivery of this ligand to the kidney. These results support our earlier mechanistic hypothesis and demonstrate the feasibility of inhibition of cis-platinum toxicity by DDTC without inhibition of the antitumor effect.