Premalignant alterations in the lipid composition and fluidity of colonic brush border membranes of rats administered 1,2 dimethylhydrazine.
Premalignant alterations in the lipid composition and fluidity of colonic brush border membranes of rats administered 1,2 dimethylhydrazine.
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给予 1,2 二甲基肼的大鼠结肠刷状缘膜的脂质成分和流动性发生癌前变化。
DOI：
10.1172/jci112380
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Dahiya,R
中科院分区：
文献类型：
--
作者：
Brasitus,TA;Dudeja,PK;Dahiya,R
二甲基肼（DMH）是一种对结肠具有选择性的强效前致癌物。为了确定大鼠结肠刷状缘膜的脂质组成和流动性是否在DMH诱导的结肠癌发生之前存在改变，将大鼠皮下注射DMH。用该药剂（20 mg/kg体重/wk）或稀释剂给药5、10和15 wk。在这些时间段处死动物，并从每组的近端和远端结肠细胞制备刷状缘膜。然后，通过稳态荧光偏振技术，使用限制受阻荧光各向异性和顺序参数值的荧光团1，6二苯基-1，3，5-己三烯（DPH）和荧光各向异性值的DL-2-（9-蒽酰基）硬脂酸和DL-12-（9-蒽酰基）硬脂酸，分别评估每个膜的流动性的“静态”和“动态”组件。提取膜脂，并通过薄层色谱和气液色谱进行分析。还使用S-腺苷-L-甲硫氨酸作为甲基供体测量这些膜中的磷脂甲基化活性。这些研究的结果表明：近端DMH处理的膜和对照膜及其脂质体的脂质组成和流动性的两个组分在所有检查的时间段都是相似的，在5、10和15周，发现远端DMH处理的膜及其脂质体的“流动性的动态组分”分别高于、相似和低于对照对应物;然而，远端DMH处理的膜及其脂质体的“流动性的静态成分”在所有三个时间段与对照制剂相似;脂质组成和磷脂甲基化活性的改变似乎是这些不同时间段“流动性的动态成分”差异的原因。
Dimethylhydrazine (DMH) is a potent procarcinogen with selectivity for the colon. To determine whether alterations in the lipid composition and fluidity of rat colonic brush border membranes existed before the development of DMH-induced colon cancer, rats were injected s.c. with this agent (20 mg/kg body weight per wk) or diluent for 5, 10, and 15 wk. Animals were killed at these time periods and brush border membranes were prepared from proximal and distal colonocytes of each group. The "static" and "dynamic" components of fluidity of each membrane were then assessed, by steady-state fluorescence polarization techniques using limiting hindered fluorescence anisotropy and order parameter values of the fluorophore 1,6 diphenyl-1,3,5-hexatriene (DPH) and fluorescence anisotropy values of DL-2-(9-anthroyl) stearic acid and DL-12-(9-anthroyl) stearic acid, respectively. Membrane lipids were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. Phospholipid methylation activity in these membranes was also measured using S-adenosyl-L-methionine as the methyl donor. The results of these studies demonstrate that: the lipid composition and both components of fluidity of proximal DMH-treated and control membranes and their liposomes were similar at all time periods examined; at 5, 10, and 15 wk the "dynamic component of fluidity" of distal DMH-treated membranes and their liposomes was found to be higher, similar, and lower, respectively, than their control counterparts; the "static component of fluidity" of distal DMH-treated membranes and their liposomes, however, was similar to control preparations at all three time periods; and alterations in the lipid composition and phospholipid methylation activities appeared to be responsible for these differences in the "dynamic component of fluidity" at these various time periods.Images