Studies on the Binding of 5,5-Diphenylhydantoin to Nucleic Acids 'In vitro' and to Rat Brain Subcellular Fractions 'In vitro' and 'In vivo'.

摘要

The binding of 5,5'-diphenylhydantoin (DPH) to nucleic acids (bovine brain RNA, rat liver ribosomal and tRNA, T. utilis RNA, and calf thymus and Escherichia coli DNA) was studied using UV spectroscopy, gel chromatography, and thermal transition profiles. Within the sensitivity of these methods it was found that there is essentially little or no interaction between DPH and nucleic acids in vitro as has been previously reported. LIttle, if any evidence of DPH intercalation with DNA was noted during thermal transition studies. DPH does not interfere with DNA reassociation. Further studies into the nature of the in vivo subcellular distribution of 14C-DPH in rat brain revealed accumulation of the radioactivity primarily in the soluble fractions. The nuclear fraction and the microsomes, containing high DNA and RNA tissue ratios, demonstrated the greatest particulate association with radioactivity at 2 and 12 hrs, respectively. This association with particulate fractions was not demonstrated after gel chromatography. These data do not support a hypothesis relating DPH binding to nucleic acids in vitro or in vivo to a possible mechanism of action of the drug.