Relative cytotoxicity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyladenine 5'-monophosphate.
The relative cytotoxicity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) were compared using wild-type and adenosine kinase (AK)-deficient baby hamster kidney somatic cell mutants. The cytotoxicity of ara-AMP to baby hamster kidney cells was dependent on the presence of AK activity since AK-deficient mutants were resistant to ara-AMP. On an equimolar basis, ara-AMP was consistently less cytotoxic than was 9-beta-D-arabinofuranosyladenine to wild-type and AK-deficient baby hamster kidney mutant cells. These findings are consistent with the common view that ara-AMP molecules do not enter mammalian cells as an intact nucleotide. Presumably, ara-AMP molecules were hydrolyzed by the nonspecific phosphatases and 5'-nucleotidase found in the serum or by the ecto-5'-nucleotidase on the outer surface of the membrane and only enter the mammalian cells as 9-beta-D-arabinofuranosyladenine.
D000248:Adenosine Kinase / Q000172:deficiency; D000818:Animals; D001088:Arabinonucleotides / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007668:Kidney; D009708:Nucleotidases / Q000378:metabolism; D014740:Vidarabine / Q000633:toxicity*; D001084:Vidarabine Phosphate / Q000633:toxicity*
D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; D000248:Adenosine Kinase; D009708:Nucleotidases; D014740:Vidarabine