Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between enzymatic activities and the degree of malignancy of human lymphomas. 404 77

Human lymphocytes lose viability when incubated in vitro with either aphidicolin, an inhibitor of DNA polymerase alpha, or with the combination of aphidicolin and deoxycoformycin (an adenosine deaminase inhibitor). Loss of viability was assayed by vital staining with fluorescein diacetate as well as examination of Wright stained preparations and the appearance of cellular debris observed using an electronic cell counter. The loss of viability was rapid with the combination of aphidicolin (2 micrograms/ml) and deoxycoformycin (1 microgram/ml) with essentially complete loss of viability after 72 hours of incubation. This drug combination produces DNA single strand breaks after 24 and 48 hours of incubation at a level equivalent to that produced by 200 or 400R of X-irradiation, respectively.
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PMID:Aphidicolin and deoxycoformycin cause DNA breaks and cell death in unstimulated human lymphocytes. 642 3

9-beta-D-Arabinofuranosyl-2-fluoroadenine (2-F-ara-A), a derivative of 9-beta-D-arabinofuranosyladenine (ara-A) that is resistant to deamination, selectively inhibits DNA synthesis and has activity against mouse leukemia L1210 comparable to that of ara-A plus the adenosine deaminase inhibitor, 2'-deoxycoformycin. To determine if these two nucleosides have similar modes of action, comparisons were made of their effects and those of their triphosphates on enzymes known to be inhibited by ara-A or 9-beta-D-arabinofuranosyladenine 5'-triphosphate. 9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-triphosphate was more effective than 9-beta-D-arabinofuranosyladenine 5'-triphosphate in inhibiting the reduction of adenosine 5'-diphosphate and cytidine 5'-diphosphate by ribonucleotide reductase from HEp-2 cells or L1210 cells. DNA polymerase alpha from L1210 cells was equally sensitive to 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-triphosphate and 9-beta-D-arabinofuranosyladenine 5'-triphosphate, and DNA polymerase beta from L1210 cells was much less sensitive to both triphosphates. S-Adenosylhomocysteine hydrolase from L1210 cells was inactivated by 2-F-ara-A and ara-A, but higher concentrations of the fluoro derivative were required. These results are consistent with 2-F-ara-A and ara-A inhibition of DNA synthesis by inhibition of ribonucleotide reductase and DNA polymerase alpha.
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PMID:Comparison of the actions of 9-beta-D-arabinofuranosyl-2-fluoroadenine and 9-beta-D-arabinofuranosyladenine on target enzymes from mouse tumor cells. 704 80