Nucleoside transport and cytosine arabinoside (araC) metabolism in human T lymphoblasts resistant to araC, thymidine and 6-methylmercaptopurine riboside.

Alteration in cellular nucleoside transport characteristics, deoxynucleoside triphosphate (dNTP) pools and araCTP formation from cytosine arabinoside (araC) were determined for human T lymphoblasts (CCRF-CEM) resistant to araC, thymidine or 6-methylmercaptopurine riboside (6-MMPR). AraC resistance was accompanied by reduced activities of deoxycytidine and thymidine kinases, lowered cellular deoxycytidine triphosphate concentration and markedly reduced formation of araCTP from araC. The ID50 values for araC, araCTP formation and dNTP levels of thymidine-resistant lymphoblasts, which exhibited reduced thymidine kinase activity, and 6-MMPR-resistant cells, with reduced adenosine kinase activity, were similar to the corresponding parameters of wild type lymphoblasts. The nucleoside transport sites density determined by nitrobenzylmercaptopurine riboside binding was comparable for araC-resistant, wild type and thymidine- or 6-MMPR-resistant lymphoblasts.