The present study was designed to elucidate the cytotoxic potential of 8 possible substituted uracilic metabolites of methylxanthines. 5-Fluorouracil (5-FU) was used as a reference uracil analogue with cytotoxic activity. Substituted uracil derivatives examined in this study did not affect the proliferative capacity of PHA-stimulated rat lymphocytes, murine L1210 leukaemia and rat chondrocytes. Caffeine had some growth inhibitory activity of extremely high concentrations (greater than 100 micrograms/ml). In vivo administration of 6-amino-5[N-methyl-formylamino]1,3-dimethyluracil (1,3,7-TAU) and 6-amino-5[N-acetylamino]3-methyluracil (7-A3-MAU) caused a transient short-lived reduction of L1210 tumour cell numbers. These observations do not appear to support the hypothesis that substituted uracils are involved in the toxicity of high doses of caffeine in rats.
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