Inhibition of ornithine decarboxylase with 2-difluoromethylornithine: reduced incidence of dimethylhydrazine-induced colon tumors in mice.
Inhibition of ornithine decarboxylase with 2-difluoromethylornithine: reduced incidence of dimethylhydrazine-induced colon tumors in mice.
复制标题
用 2-二氟甲基鸟氨酸抑制鸟氨酸脱羧酶：降低二甲基肼诱导的小鼠结肠肿瘤的发生率。
作者：
A. Kingsnorth;W. W. King;K. Diekema;P. McCann;J. Ross;R. Malt
2-二氟甲基鸟氨酸（DFMO）给予1，2-二甲基肼（DMH）治疗的小鼠，以减少结肠多胺水平和粘膜增生。在整个实验过程中，小鼠接受含1%DFMO的饮用水，并每周注射DMH（20 mg/kg），持续28周。DFMO灭活了93%的结肠鸟氨酸脱羧酶活性。尽管DMH处理在第28周时未诱导结肠鸟氨酸脱羧酶活性，但在DMH处理的小鼠中腐胺含量增加了31%（p <0.01）。同时用DFMO处理降低腐胺含量（42 - 63%）和亚精胺含量（27 - 38%），但提高精胺含量（18 - 22%）。在单独用DMH处理的第28周，RNA含量增加8.6%（p小于0.01），DNA含量增加10%（p小于0.01），DNA比活性增加24%（p小于0.01），隐窝深度增加20%（p小于0.01），但在接受DMH和DFMO的小鼠中没有增加。在28周时，17只单独用DMH治疗的小鼠中有13只（76%）有组织学证实的结肠癌;在用DMH和DFMO治疗的小鼠中，18只小鼠中有两只（11%）有结肠肿瘤。在整个实验过程中，16只DMH处理的小鼠中发生了50例结肠癌（平均3.12个肿瘤/小鼠）;用DMH和DFMO处理的3只小鼠共发生了3例结肠癌（p小于0.001）。DFMO治疗后结肠多胺水平的降低可防止DMH诱导的增殖性变化并降低肿瘤的发生率。
2-Difluoromethylornithine (DFMO) was administered to 1,2-dimethylhydrazine (DMH)-treated mice to reduce colonic polyamine levels and mucosal hyperplasia. Mice received 1% DFMO in drinking water throughout the experiment and were given injections of DMH (20 mg/kg) weekly for 28 weeks. DFMO inactivated 93% of colonic ornithine decarboxylase activity. Although DMH treatment did not induce colonic ornithine decarboxylase activity by Week 28, the putrescine content was increased 31% in DMH-treated mice (p less than 0.01). Concurrent treatment with DFMO depressed putrescine content (42 to 63%) and spermidine content (27 to 38%), but it increased spermine content (18 to 22%). At Week 28 of treatment with DMH alone, RNA content was increased 8.6% (p less than 0.01), DNA content 10% (p less than 0.01), DNA specific activity 24% (p less than 0.01), and crypt depth 20% (p less than 0.01), but not in mice receiving DMH and DFMO. At 28 weeks, 13 of 17 mice (76%) treated with DMH alone had histologically confirmed colon cancers; of mice treated with DMH and DFMO, two of 18 (11%) had colonic tumors. Throughout the experiment, 50 colon cancers developed in 16 DMH-treated mice (mean, 3.12 tumors/mouse); three mice treated with DMH and DFMO developed three colon cancers total (p less than 0.001). Reduction of colonic polyamine levels after DFMO treatment prevents proliferative changes induced by DMH and reduces the incidence of tumors.
α-二氟甲基鸟氨酸（一种鸟氨酸脱羧酶抑制剂）增强 1,3-双（2-氯乙基）-1-亚硝基脲的抗肿瘤治疗作用。
影响因子：
11.2
作者：
Marton,LJ;Levin,VA;Hervatin,SJ;Koch-Weser,J;McCann,PP;Sjoerdsma,A
通讯作者：
Sjoerdsma,A