In vitro and in vivo cytotoxicity of possible uracil metabolites of methylxanthines

Giuseppe Peri, Nadia Polentarutti, Stefania Filippeschi, Carmela Malfiore, Giuseppina Amato, Stefano Pepe, Maurizio Bonati, Silvio Garattini, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review


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 (>100 μ g/ml). In vivo administration of 6-amino-5[N-methyl-formylamino],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.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalToxicology Letters
Issue number1-2
Publication statusPublished - 1983


  • 1,3,7-TAU
  • 1,3,7-TMX
  • 1,3-DAU
  • 1,7-DAU
  • 1-MAU
  • 3,7-DAU
  • 3-dimethyluracil
  • 3-MAU
  • 5-fluorouracil
  • 5-FU
  • 6-amino-5--[N-methyl-formylamino] 3-methyluracil
  • 6-amino-5-[N-acetylamino] 3-methyluracil
  • 6-amino-5-[N-formylamino]3-methyluracil
  • 6-amino-5-[N-formylamino]l
  • 6-amino-5-[N-formylamino]l-methyluracil
  • 6-amino-5-[N-methyl-formylamino]l,3-dimethyluracil
  • 6-amino-5-[N-methyl-formylamino]l-methyluracil
  • 6-amino-5-[N-methyl-formylamino]uracil
  • 7-A3-MAU
  • 7-MAU
  • caffeine
  • FBS
  • foetal bovine serum
  • PHA
  • phytohaemagglutinin
  • [H]methyl-thymidine
  • [H]TdR

ASJC Scopus subject areas

  • Toxicology


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