LACK OF DIHYDROFOLATE-REDUCTASE IN HUMAN-TUMOR AND LEUKEMIA-CELLS INVIVO
LACK OF DIHYDROFOLATE-REDUCTASE IN HUMAN-TUMOR AND LEUKEMIA-CELLS INVIVO
复制标题
DOI：
10.1089/cdd.1985.2.133
复制
发表时间：
1985-01-01
期刊：
影响因子：
--
通讯作者：
PETERSON, DW
中科院分区：
文献类型：
--
作者：
KAMEN, BA;NYLEN, PA;PETERSON, DW
二氢叶酸还原酶(DHFR)是甲氨蝶呤和其他抗叶酸化合物的主要靶标，在体外培养的人细胞系中的浓度是在人肿瘤或原位获得的细胞中的100-200倍。然而，体外测定的人细胞株的DHFR含量相当于体外测量的啮齿动物肿瘤株。用[~3H]氨甲喋呤结合、[~3H]二氢叶酸还原为[~3H]四氢叶酸、用抗DHFR的单特异性抗血清免疫沉淀的方法对酶进行定量。进一步的研究表明，只有肝脏样本中含有大量的DHFR活性抑制物。有人推测，新鲜人体组织中DHFR的低水平反映了细胞周转率的低，或者相反，体外和动物组织中的高水平反映了由于培养基和准备好的饲料中的叶酸水平高而产生的高水平的酶。
Dihydrofolate reductase (DHFR), the main target for methotrexate and other antifolate compounds was found to be present in 100-200 times higher concentration in human cell lines grown in vitro than in human tumors or cells obtained in situ. The DHFR content of human cell lines in vitro however, were equivalent to rodent tumor lines also measured in vitro. The enzyme as quantitated by [3H]methotrexate binding; [3H]dihydrofolate reduction to [3H]tetrahydrofolate; and immunoprecipitation with a monospecific anti-serum to DHFR. Additional studies revealed only a liver sample to contain significant amounts of an inhibitor of DHFR activity. It is postulated either that low levels of DHFR in fresh human tissue reflect low cell turnover or conversely that high levels in vitro and in animal tissues reflect high levels of enzyme due to selection because of high levels of folic acid in culture medium and prepared feeds.