Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deoxyadenosine toxicity toward lymphocytes may produce immune dysfunction in patients with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. The relationship between endogenous deoxynucleoside synthesis in adenosine deaminase-deficient cells and sensitivity to adenosine and deoxyadenosine toxicity is unclear. The human histiocytic lymphoma cell line (DHL-9) naturally lacks adenosine deaminase, and has minimal levels of thymidine kinase. Dividing DHL-9 cells excrete deoxyadenosine and thymidine into the extracellular space. The present experiments have analyzed nucleoside synthesis and excretion in a mutagenized clone of DHL-9 cells, selected for increased resistance to deoxyadenosine toxicity. The deoxyadenosine-resistant cells excreted both deoxyadenosine and thymidine at a 6-7-fold higher rate than wild-type lymphoma cells. The deoxyadenosine overproduction was accompanied by a reduced ability to form dATP from exogenous deoxyadenosine, and a 2.5-fold increase in ribonucleotide reductase activity. The pace of adenosine excretion, the growth rate, and the levels of multiple other enzymes involved in deoxyadenosine and adenosine metabolism were equivalent in the two cell types. These results suggest that the excretion of deoxyadenosine and thymidine, but not adenosine, is exquisitely sensitive to alterations in the rate of endogenous deoxynucleotide synthesis. Apparently, small changes in deoxynucleotide synthesis can significantly influence cellular sensitivity to deoxyadenosine toxicity.
 ...
PMID:Deoxynucleoside overproduction in deoxyadenosine-resistant, adenosine deaminase-deficient human histiocytic lymphoma cells. 637 66

The activities of thymidine kinase (TK) isoenzyme 1 and 2 were examined in extracts of human benign or malignant lymphoid tissue and correlated with degrees of morphological differentiation. TK2 activity occurred in peripheral blood lymphocytes of normal individuals, patients with chronic lymphocytic leukemia, or solid lymphoid tissue, exhibiting either nonneoplastic histological findings or those of diffuse well-differentiated lymphocytic lymphoma. TK1 activity occurred in solid, non-Hodgkin's lymphoma tissue, exhibiting lesser degrees of cellular differentiation, or in peripheral blood lymphocytes of patients with clinical aggressive chronic lymphocytic leukemia or lymphosarcoma leukemia. In non-Hodgkin's lymphoma tissue, the range of TK1 activities correlated broadly with the Rappaport classification, with higher values occurring in tissue exhibiting changes of diffuse poorly differentiated lymphocytic lymphoma or diffuse histiocytic lymphoma.
 ...
PMID:Thymidine kinase isoenzymes in human malignant lymphoma. 744 15