REVERSAL OF 6-MERCAPTOPURINE AND 6-METHYLMERCAPTOPURINE RIBONUCLEOSIDE CYTOTOXICITY BY AMIDOIMIDAZOLE CARBOXAMIDE RIBONUCLEOSIDE IN MOLT-F4HUMAN-MALIGNANT T-LYMPHOBLASTS

Cytotoxicity of 6-mercaptopurine (6MP) and 6-methylmercaptopurine ribo nucleoside (Me-MPR) was studied in Molt F4 human malignant lymphoblast s. Both drugs are converted into methyl-thioIMP (Me-tIMP), which inhib its purine de novo synthesis. Addition of amidoimidazole carboxamide r ibonucleoside (AICAR) circumvented inhibition of purine de novo synthe sis, and thus partly prevented 6MP and Me-MPR cytotoxicity. Purine nuc leotides, and especially adenine nucleotides, were recovered by additi on of AICAR. Under these conditions, Me-tIMP formation decreased. The results of this study indicate that formation of Me-tIMP may be import ant for 6MP cytotoxicity in Molt F4 cells. These data suggest that dep letion of adenine nucleotides is the main cause for Me-tIMP cytotoxici ty.