Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
|
pubmed:dateCreated |
1995-8-29
|
pubmed:abstractText |
Different cell lines, 2 from human colon carcinoma (LoVo and HT29) and 1 from Chinese hamster ovary (CHO K-I), were examined to assess the effect of deoxycoformycin (dCF), an inhibitor of adenosine deaminase (ADA), and 2'-deoxyadenosine (dAdo) on their growth. When used alone, neither dCF or dAdo were cytotoxic for the 3 cell lines, while their combination caused inhibition of cell growth, with the following sensitivity: CHO K-I > LoVo > HT29. We studied the pattern of enzymatic activities involved in the metabolism of dAdo in the 3 cell lines. The phosphorylation of dAdo by adenosine kinase appears to play a central role in the toxicity of the deoxynucleoside in combination with dCF. In fact, CHO K-I cells, which are the most sensitive, possess the highest level of this enzyme. Moreover, the cytotoxic effect was almost completely reversed in the 3 cell lines when inhibitors of adenosine kinase, such as 5'-amino-5'-deoxyadenosine and iodotubercidine, were added to the culture medium together with dCF and dAdo. In addition, baby hamster kidney (BHK) adenosine-kinase-deficient (AK-) cells were highly resistant to this treatment. Uptake inhibition of dAdo using dipyridamole also caused reversal of the toxicity. The AMP and deoxyAMP dephosphorylating activities, much lower in the CHO K-I cells, also appear to play a central role in the toxicity of dAdo when adenosine deaminase is inhibited. However, our data suggest that other factors may modulate the toxic effect, such as S-adenosyl-homocysteine-hydrolase inhibition by dAdo at high concentrations.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2'-deoxyadenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenosines,
http://linkedlifedata.com/resource/pubmed/chemical/Dipyridamole,
http://linkedlifedata.com/resource/pubmed/chemical/Pentostatin,
http://linkedlifedata.com/resource/pubmed/chemical/Purines,
http://linkedlifedata.com/resource/pubmed/chemical/S-Adenosylhomocysteine
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jul
|
pubmed:issn |
0020-7136
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
17
|
pubmed:volume |
62
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
176-83
|
pubmed:dateRevised |
2007-7-24
|
pubmed:meshHeading |
pubmed-meshheading:7622293-Adenosine Kinase,
pubmed-meshheading:7622293-Antimetabolites, Antineoplastic,
pubmed-meshheading:7622293-Cell Division,
pubmed-meshheading:7622293-Colonic Neoplasms,
pubmed-meshheading:7622293-Deoxyadenosines,
pubmed-meshheading:7622293-Dipyridamole,
pubmed-meshheading:7622293-Drug Synergism,
pubmed-meshheading:7622293-Humans,
pubmed-meshheading:7622293-Pentostatin,
pubmed-meshheading:7622293-Purines,
pubmed-meshheading:7622293-S-Adenosylhomocysteine,
pubmed-meshheading:7622293-Tumor Cells, Cultured
|
pubmed:year |
1995
|
pubmed:articleTitle |
Purine enzyme profile in human colon-carcinoma cell lines and differential sensitivity to deoxycoformycin and 2'-deoxyadenosine in combination.
|
pubmed:affiliation |
Dipartimento di Fisiologia e Biochimica, Università di Pisa, Italy.
|
pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|