A. MacKinney, R. Vyas
Jul 1, 1975
Citations
0
Influential Citations
4
Citations
Quality indicators
Journal
Toxicology and applied pharmacology
Abstract
Abstract In order to explore the mode of action of 5,5-diphenylhydantoin (DPH), we studied the inhibitory effect of compounds with related hydroxylamine or carbamate structures on DNA and protein synthesis of proliferating human lymphocytes. A series of 3-hydroxyhydantoins was weaker than the parent DPH, indicating that the N3 hydroxyl group did not activate the compounds, whereas substitutions at the C5 position generally diminished activity. Parahydroxylation of the benzene ring enhanced inhibition of DNA and protein synthesis. Acetoxylation of the N3 position of diphenylhydantoin greatly increased its potency; acetoxylation of 2-acetylaminofluorene, a known carcinogen, had a similar effect. 1-Acetyl-3-acetoxy-5,5-diphenylhydantoin inhibited DNA synthesis to approximately the same degree as N-acetoxy-2-acetyl aminofluorene, xylyl phenyl carbamate, hydroxyurea, and hydroxylamine. This derivative of DPH illustrates the central role of the N3 position in metabolic reactions with lymphocytes. The contribution of this derivative to lymphomagenesis is not known.