Relationship between phosphorylation and cytotoxicity of 2-chloroadenosine and 6-methylmercaptopurine riboside in human cells.

2-Chloroadenosine but not 6-methylmercaptopurine riboside was phosphorylated by adenosine kinase negative human B cells, and the adenosine negative cells were resistant to 6-methylmercaptopurine riboside but not to 2-chloroadenosine. Phosphorylation of 6-methylmercaptopurine was totally dependent on adenosine kinase, but 2-chloroadenosine seemed to be phosphorylated by other enzyme(s) as well. The cytotoxicity of both of these analogs depends on the phosphorylation.