TY - JOUR
T1 - S-Adenosylhomocysteine Hydrolase Inhibition in Deoxyadenosine-Treated Human T-Lymphoblasts and Resting Peripheral Blood Lymphocytes
AU - Kefford, Richard F.
AU - Helmer, Megan A.
AU - Fox, Richard M.
PY - 1982/9/1
Y1 - 1982/9/1
N2 - The pattern of inhibition and recovery of intracellular S-adenosylhomocysteine hydrolase (AdoHcyase) activity induced by cytotoxic concentrations of 2’-deoxyadenosine (dAdo) in the presence of the adenosine deaminase inhibitor erythro-9-[3-(2-hydroxynonyl)]adenine was studied in cultured human T-lymphoblasts (CCRF-CEM and -HSB), Epstein-Barr virus-transformed B-lymphoblasts (JP and RDG), and resting peripheral blood lymphocytes. In the presence of 5 derythro-9-[3-(2-hydroxynonyl)]adenine the AdoHcyase activity was inhibited 50% after 1 hr of incubation by 3, 10, and 30 dAdo for B-lymphoblasts, T-lymphoblasts, and peripheral blood lymphocytes, respectively, while cytotoxicity (to 50% of controls) was effected by 600,3, and 1 µM dAdo, respectively. Cytostatic concentrations of dAdo, which induce G1-phase arrest in T-lymphoblasts, inhibited AdoHcyase to 30% of control at 4 hr, after which recovery to normal levels occurred over 24 hr. Coincubation with 50 µM 2#-deoxycytidine, which protects these cells from both G1-phase arrest and growth inhibition by dAdo, had no effect on the pattern of inhibition of AdoHcyase activity. Epstein-Barr virus-transformed B-lymphoblasts exposed to the same concentrations of dAdo were not growth inhibited but displayed patterns of AdoHcyase inhibition closely similar to those seen in T-lymphoblasts. Coincubation with 20 µM 2’-deoxycytidine, despite its protective effect againt dAdo cytotoxicity, had no effect on the pattern of AdoHcyase inhibition in resting peripheral blood lymphocytes induced by 10 µM dAdo and 5 erythro-9-[3-(2-hydroxynonyl)]adenine over a 72-hr period. The lack of correlation between cytotoxicity and AdoHcyase inhibition in human lymphoid cells suggest that other mechanisms may account for the toxic effects of dAdo in these cells.
AB - The pattern of inhibition and recovery of intracellular S-adenosylhomocysteine hydrolase (AdoHcyase) activity induced by cytotoxic concentrations of 2’-deoxyadenosine (dAdo) in the presence of the adenosine deaminase inhibitor erythro-9-[3-(2-hydroxynonyl)]adenine was studied in cultured human T-lymphoblasts (CCRF-CEM and -HSB), Epstein-Barr virus-transformed B-lymphoblasts (JP and RDG), and resting peripheral blood lymphocytes. In the presence of 5 derythro-9-[3-(2-hydroxynonyl)]adenine the AdoHcyase activity was inhibited 50% after 1 hr of incubation by 3, 10, and 30 dAdo for B-lymphoblasts, T-lymphoblasts, and peripheral blood lymphocytes, respectively, while cytotoxicity (to 50% of controls) was effected by 600,3, and 1 µM dAdo, respectively. Cytostatic concentrations of dAdo, which induce G1-phase arrest in T-lymphoblasts, inhibited AdoHcyase to 30% of control at 4 hr, after which recovery to normal levels occurred over 24 hr. Coincubation with 50 µM 2#-deoxycytidine, which protects these cells from both G1-phase arrest and growth inhibition by dAdo, had no effect on the pattern of inhibition of AdoHcyase activity. Epstein-Barr virus-transformed B-lymphoblasts exposed to the same concentrations of dAdo were not growth inhibited but displayed patterns of AdoHcyase inhibition closely similar to those seen in T-lymphoblasts. Coincubation with 20 µM 2’-deoxycytidine, despite its protective effect againt dAdo cytotoxicity, had no effect on the pattern of AdoHcyase inhibition in resting peripheral blood lymphocytes induced by 10 µM dAdo and 5 erythro-9-[3-(2-hydroxynonyl)]adenine over a 72-hr period. The lack of correlation between cytotoxicity and AdoHcyase inhibition in human lymphoid cells suggest that other mechanisms may account for the toxic effects of dAdo in these cells.
UR - http://www.scopus.com/inward/record.url?scp=0019954277&partnerID=8YFLogxK
M3 - Article
C2 - 6980705
AN - SCOPUS:0019954277
SN - 0008-5472
VL - 42
SP - 3822
EP - 3827
JO - Cancer Research
JF - Cancer Research
IS - 9
ER -