人肿瘤和白血病细胞体内缺乏二氢叶酸还原酶。

B A Kamen, P A Nylen, V M Whitehead, H T Abelson, B J Dolnick, D W Peterson
{"title":"人肿瘤和白血病细胞体内缺乏二氢叶酸还原酶。","authors":"B A Kamen,&nbsp;P A Nylen,&nbsp;V M Whitehead,&nbsp;H T Abelson,&nbsp;B J Dolnick,&nbsp;D W Peterson","doi":"10.1089/cdd.1985.2.133","DOIUrl":null,"url":null,"abstract":"<p><p>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 was 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.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"2 2","pages":"133-8"},"PeriodicalIF":0.0000,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1985.2.133","citationCount":"36","resultStr":"{\"title\":\"Lack of dihydrofolate reductase in human tumor and leukemia cells in vivo.\",\"authors\":\"B A Kamen,&nbsp;P A Nylen,&nbsp;V M Whitehead,&nbsp;H T Abelson,&nbsp;B J Dolnick,&nbsp;D W Peterson\",\"doi\":\"10.1089/cdd.1985.2.133\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 was 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.</p>\",\"PeriodicalId\":77686,\"journal\":{\"name\":\"Cancer drug delivery\",\"volume\":\"2 2\",\"pages\":\"133-8\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1985-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1089/cdd.1985.2.133\",\"citationCount\":\"36\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer drug delivery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1089/cdd.1985.2.133\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer drug delivery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/cdd.1985.2.133","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 36

摘要

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点,在体外培养的人类细胞系中的浓度比在原位获得的人类肿瘤或细胞中的浓度高100-200倍。而体外培养的人细胞系的DHFR含量与体外检测的啮齿动物肿瘤细胞系相当。通过[3H]甲氨蝶呤结合,[3H]二氢叶酸还原为[3H]四氢叶酸,以及DHFR单特异性抗血清免疫沉淀来定量酶。进一步的研究显示,只有一个肝脏样本含有大量的DHFR活性抑制剂。据推测,新鲜人体组织中的低水平DHFR反映了低细胞更新,或者相反,体外和动物组织中的高水平DHFR反映了由于培养基和制备饲料中叶酸含量高而进行的选择而产生的高水平酶。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lack of dihydrofolate reductase in human tumor and leukemia cells in vivo.

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 was 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信