肝脏致癌物甲吡咯烷在费希尔大鼠体内的分布及其与大分子的相互作用。
Distribution of the liver carcinogen methapyrilene in Fischer rats and its interaction with macromolecules.
作者信息
Lijinsky W, Muschik G M
出版信息
J Cancer Res Clin Oncol. 1982;103(1):69-73. doi: 10.1007/BF00410307.
The anti-histaminic drug methapyrilene hydrochloride, which induces liver tumors in ras, was labeled with tritium by exchange and administered at a does of 21 mg containing 700 microCi to each of 15 male Fischer rats. At 1 h, 6 h, 14 h, 24 h, and 44 h after treatment three rats were killed and their livers, pancreas, kidneys, and lungs were removed. The pooled organs were homogenized and DNA, RNA, and soluble protein were isolated from each. The extent of interaction of radioactive methapyrilene with liver nucleic acids was exceedingly small and did not differ significantly from the binding to nucleic acids in kidney, lung, or pancreas, which are not target organs of this carcinogen in rats. Binding of radioactivity to soluble proteins of the liver was considerable and substantially greater than in the other organs. If the mechanism of carcinogenic action of methapyrilene involves covalent interaction with DNA this must be at a very low and highly specific level.
抗组胺药物盐酸美吡拉敏可在大鼠中诱发肝脏肿瘤，通过交换法用氚标记该药物，并以每只15只雄性Fischer大鼠21毫克（含700微居里）的剂量给药。治疗后1小时、6小时、14小时、24小时和44小时，处死3只大鼠，取出它们的肝脏、胰腺、肾脏和肺。将合并的器官匀浆，从每个器官中分离出DNA、RNA和可溶性蛋白质。放射性美吡拉敏与肝脏核酸的相互作用程度极小，与在肾脏、肺或胰腺中与核酸的结合无显著差异，而这些器官并非该致癌物在大鼠中的靶器官。放射性与肝脏可溶性蛋白质的结合相当可观，且大大高于其他器官。如果美吡拉敏的致癌作用机制涉及与DNA的共价相互作用，那么这种相互作用必定处于非常低且高度特异的水平。
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