Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine.
Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine.
复制标题
5-羟甲基脱氧尿苷的毒理学和抗肿瘤研究。
DOI：
10.1016/0041-008x(85)90140-1
复制
发表时间：
1985
影响因子：
3.8
通讯作者：
A. Paterson
中科院分区：
文献类型：
--
作者：
J. B. Meldrum;V. S. Gupta;N. Lowes;A. Paterson
研究了5-羟甲基脱氧尿苷（HMUdR）对瑞士白小鼠的毒性作用。检查病理、血液学和临床化学参数。单次给药高达2000 kg/kg的HMUdR对小鼠未观察到全身毒性。每天以200 mg/kg剂量给予HMUdR 15天，小鼠出现体重减轻、毛糙、腹泻、腹部肿胀、虚弱、嗜睡，死亡率为20%。所有接受HMUdR治疗的小鼠血液学和临床化学指标均在正常范围内。尸检时，所有器官大体正常，但治疗小鼠组织的显微镜检查显示，小肠绒毛变短、增厚，肠隐窝上皮细胞出现核空泡化和坏死，肝细胞出现一些细胞质空泡化，导致核边缘。所有组织学病变在停止治疗后都是可逆的。HMUdR在细胞培养中对小鼠L1210和L5178Y白血病有活性。与未处理的细胞相比，抑制细胞生长50%所需的浓度分别为2 μm和4 μm。当HMUdR以50、100或200 mg/kg的每日5次剂量给药给植入L1210细胞的小鼠时，寿命比安慰剂治疗的对照组增加了20%、30%或33%。
Toxic effects of 5-hydroxymethyldeoxyuridine (HMUdR) were studied in white Swiss mice. Pathological, hematological, and clinical chemistry parameters were examined. Systemic toxicity was not observed in mice after ip administration of HMUdR in single doses up to 2000 kg/kg. Mice administered HMUdR daily for 15 days at 200 mg/kg, ip, manifested loss of weight, rough hair coat, diarrhea, swollen abdomens, weakness, lethargy, and a 20% mortality rate. Hematological and clinical chemistry parameters of all mice receiving HMUdR were within normal limits. At necropsy, all organs were grossly normal but microscopic examination of tissues of treated mice revealed the presence of shortened, thickened villi in the small intestine, nuclear vacuolation and necrosis of intestinal crypt epithelial cells, and some cytoplasmic vacuolation causing nuclear margination in hepatocytes. All histological lesions were reversible with cessation of treatment. HMUdR was active against murine L1210 and L5178Y leukemias in cell culture. The concentrations required to inhibit cell growth 50% compared to untrated cells was 2 and 4 μm, respectively. When HMUdR was administered ip at 50, 100, or 200 mg/kg in five daily doses to mice implanted with L1210 cells, life spans increased 20, 30, or 33% over placebo-treated controls.