Correlation of cytotoxicity with total intracellular exposure to 9-beta-D-arabinofuranosyladenine 5'-triphosphate.
The mechanism by which 9-beta-D-arabinofuranosyladenine produces cell death has been studied extensively, but the details remain controversial. The results presented here describe an evaluation of 9-beta-D-arabinofuranosyladenine-induced cytotoxicity in terms of the product of the total amount of the active 5'-triphosphate metabolite, 9-beta-D-arabinofuranosyladenine 5'-triphosphate (ara-ATP), which accumulated in the cells, and the duration of the exposure expressed in units of ara-ATP microM-hr. It was demonstrated that a strong correlation exists between these parameters which was not affected by the rate of accumulation of ara-ATP. In addition, inhibition of 9-beta-D-arabinofuranosyladenine deamination by 2'-deoxycoformycin did not alter the relationship between cell death and total intracellular exposure to ara-ATP. The consistency of this relationship both within and between experiments indicates that the quantitation of the total cellular exposure to ara-ATP is useful in predicting cytotoxicity.
D000818:Animals; D001088:Arabinonucleotides / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D007700:Kinetics; D010053:Ovary; D015649:Pentostatin; D014740:Vidarabine / Q000378:metabolism / Q000494:pharmacology*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; D003070:Coformycin; C000101:ara-ATP; D015649:Pentostatin; D014740:Vidarabine