Red blood cell polyamine levels and host toxicity during continuous alpha-difluoromethylornithine infusion.
Red blood cell polyamine levels and host toxicity during continuous alpha-difluoromethylornithine infusion.
复制标题
连续输注α-二氟甲基鸟氨酸期间红细胞多胺水平和宿主毒性。
DOI：
10.1002/ijc.2910380215
复制
发表时间：
1986
影响因子：
6.4
通讯作者：
Nishioka,K
中科院分区：
文献类型：
--
作者：
Ota,DM;GrossieJr,VB;Ajani,JA;Stephens,LC;Nishioka,K
测定连续α-二氟甲基鸟氨酸（DFMO）输注对红细胞（RBC）多胺水平、宿主毒性和肿瘤生长的剂量效应。患有和未患有可移植甲基胆蒽诱导肉瘤的雄性大鼠静脉注射0.45% NaCl或DFMO，剂量为500 mg、1，000 mg或2，000 mg/kg体重/天，持续6或12天。给药12天后，观察到肿瘤生长的剂量相关抑制。宿主胴体重量、摄食量、血浆白蛋白、红细胞压积或白色血细胞计数无变化。血小板抑制与1，000和2，000 mg剂量和12天治疗相关。小肠的形态测定显示，在2，000 mg剂量下，十二指肠和空肠中的绒毛轻度但显著缩短，但没有动物发生腹泻。500 mg DFMO剂量降低了肿瘤生长速率，而不会诱导血小板抑制或改变肠道形态。在所有剂量下均观察到RBC腐胺水平降低。RBC亚精胺水平随500 mg剂量增加而升高。与对照组相比，所有剂量组的RBC精胺水平均较高。这些结果表明，血小板减少症是连续DFMO输注的主要剂量限制性副作用，但在500 mg/kg体重/天剂量下未发生。
The dose effects of continuous alpha‐difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene‐induced sarcoma received intravenously either 0.45% NaCI or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose‐related inhibition of tumor growth was noted after the 12‐day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet supression was associated with the 1,000‐ and 2,000‐mg doses with the 12‐day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000‐mg dose, but none of the animals developed diarrhea. The 500‐mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500‐mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose‐limiting side‐effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day.