| pubmed-article:1707752 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C1517631 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C0001407 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C0012892 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C0035547 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C1523924 | lld:lifeskim |
| pubmed-article:1707752 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:1707752 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:1707752 | pubmed:dateCreated | 1991-5-17 | lld:pubmed |
| pubmed-article:1707752 | pubmed:abstractText | 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-adenine (Cl-F-ara-A) has activity against the P388 tumor in mice on several different schedules. Biochemical studies with a chronic myelogenous leukemia cell line (K562) grown in cell culture have been done in order to better understand its mechanism of action. Cl-F-ara-A was a potent inhibitor of K562 cell growth. Only 5 nM inhibited K562 cell growth by 50% after 72 h of continuous incubation. The 5'-triphosphate of Cl-F-ara-A was detected by strong anion exchange chromatography of the acid-soluble extract of K562 cells incubated with Cl-F-ara-A. Competition studies with natural nucleosides suggested that deoxycytidine kinase was the enzyme responsible for the metabolism to the monophosphate. Incubation of K562 cells for 4 h with 50 nM Cl-F-ara-A inhibited the incorporation of [3H]thymidine into the DNA by 50%. Incubation with 0.1, 1, or 10 microM Cl-F-ara-A for 4 h depressed dATP, dCTP, and dGTP pools but did not affect TTP pools. Similar inhibition of deoxyribonucleoside triphosphate pools was seen after incubation with 2-chloro-2'-deoxyadenosine. Both Cl-F-ara-ATP and Cl-dATP potently inhibited the reduction of ADP to dADP in crude extracts of K562 cells (concentration producing 50% inhibition, 65 nM). The effect of Cl-F-ara-ATP on human DNA polymerases alpha, beta, and gamma isolated from K562 cells grown in culture was determined and compared with those of Cl-dATP and 9-beta-D-arabinofuranosyl-2-fluoroadenine triphosphate (F-ara-ATP). Cl-F-ara-ATP was a potent inhibitor of DNA polymerase alpha. Inhibition of DNA polymerase alpha was competitive with respect to dATP (Ki of 1 microM). The three analogue triphosphates were incorporated into the DNA by DNA polymerase alpha as efficiently as dATP. The incorporation of Cl-F-ara-AMP inhibited the further elongation of the DNA chain, similarly to that seen after the incorporation of F-ara-AMP. Extension of the DNA chain after the incorporation of Cl-dAMP was not inhibited as much as it was with either Cl-F-ara-AMP or F-ara-AMP. Cl-F-ara-ATP was not a potent inhibitor of DNA polymerase beta, DNA polymerase gamma, or DNA primase.(ABSTRACT TRUNCATED AT 400 WORDS) | lld:pubmed |
| pubmed-article:1707752 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:language | eng | lld:pubmed |
| pubmed-article:1707752 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:1707752 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:1707752 | pubmed:month | May | lld:pubmed |
| pubmed-article:1707752 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:ChangC HCH | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:MontgomeryJ... | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:RoseL MLM | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:BennettL... | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:BrockmanR WRW | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:ShaddixS CSC | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:ShortnacyA... | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:WhiteE LEL | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:ParkerW BWB | lld:pubmed |
| pubmed-article:1707752 | pubmed:author | pubmed-author:SecristJ... | lld:pubmed |
| pubmed-article:1707752 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:1707752 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:1707752 | pubmed:volume | 51 | lld:pubmed |
| pubmed-article:1707752 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:1707752 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:1707752 | pubmed:pagination | 2386-94 | lld:pubmed |
| pubmed-article:1707752 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:meshHeading | pubmed-meshheading:1707752-... | lld:pubmed |
| pubmed-article:1707752 | pubmed:year | 1991 | lld:pubmed |
| pubmed-article:1707752 | pubmed:articleTitle | Effects of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5'-triphosphate. | lld:pubmed |
| pubmed-article:1707752 | pubmed:affiliation | Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35205. | lld:pubmed |
| pubmed-article:1707752 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:1707752 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:1707752 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:1707752 | lld:pubmed |
