Altered cell cycle distributions of cultured human lymphoblasts during cytotoxicity related to adenosine deaminase inhibition.
Serial-flow cytometric analysis of DNA content of T lymphoblasts (MOLT-4) and B lymphoblasts (MGL-8) was performed to correlate the cytotoxic properties of adenosine deaminase inhibition with alterations of DNA synthesis and disruptions of the cell cycle. The addition of deoxyadenosine up to 50 mumol/L potently decreased the growth of T lymphoblasts, and these changes were enhanced with the addition of 100 mumol/L homocysteine thiolactone. These conditions caused a virtual absence of cells from S and G2M phases after 24 hours. The DNA distribution was similar in cells cultured for 24 hours in 50 mumol/L deoxyguanosine or 2.5 mumol/L hydroxyurea. These observations suggested accumulation of cells in the G1 phase. T lymphoblasts cultured with up to 50 mumol/L adenosine had a substantial decrease in growth, which was not modified by the addition of homocysteine thiolactone. Cell cycle distributions of T lymphoblasts cultured for 24 to 48 hours under these conditions showed mild decreases in the G2M population. The addition of adenosine up to 50 mumol/L decreased the growth of B lymphoblasts, and these changes were enhanced by the addition of 100 mumol/L homocysteine thiolactone. These conditions induced mild decreases in the S-phase population in B lymphoblasts. The addition of deoxyadenosine, even with homocysteine thiolactone, did not modify growth in B lymphoblasts and the cell-cycle distributions were indistinguishable from distributions of control populations after 24 and 48 hours. The observations provide independent support for a reduction of DNA synthesis associated with cytotoxicity during adenosine-deaminase inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
D058892:Adenosine Deaminase Inhibitors; D001402:B-Lymphocytes / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects
D058892:Adenosine Deaminase Inhibitors; D004247:DNA; D012435:S-Adenosylhomocysteine; D009700:Nucleoside Deaminases