Cytotoxicity of arabinofuranosyladenine and erythro-9-(2-hydroxy-3-nonyl) adenine to Epstein-Barr virus producer and nonproducer lymphoma cells in culture

Adenine arabinoside (ara-A) at a concentration of 5-10 μg/ml inhibited the multiplication of two Epstein-Barr virus (EBV) producer lymphoblastoid cell lines B.95-8 and P3HR-1. The nonproducer EBV genome carrier cell line, Raji, and the EBV negative cell line, Ramos, were not significantly affected. The cytotoxicity of ara-A to Ramos, Raji and P3HR-1 cells increased in the presence of 1.10^-5M erythro-9-(2-hydroxy-3-nony)adenine (EHNA), an inhibitor of adenosine deaminase. EHNA alone was noncytotoxic and even had a mild stimulatory effect on cell multiplication. The level of adenosine deaminase in Raji and Ramos cells was similar to that observed in human cord blood lymphocytes, as determined by starch gel electrophoresis. A low level of adenosine deaminase was detected in P3HR-1 cells and the enzyme was absent from B.95-8 cells. These findings indicate that in the absence of adenosine deaminase, ara-A cytotoxicity increased. Ara-A (5 μg/ml) and EHNA (1.10^-5M) had no effect on human cord blood lymphocytes stimulated by phytohemagglutinin as measured by (³H)thymidine uptake, but had some effect on protein A-stimulated lymphocytes. Ara-A however, inhibited the transformation of human cord blood lymphocytes by EBV, which EHNA did not inhibit. The synthesis of EBV capsid antigen in B.95-8 cells was also inhibited by ara-A and slightly stimulated by EHNA.