BINDING OF METABOLITES FORMED FROM AMINOSTILBENE DERIVATIVES TO NUCLEIC-ACIDS IN THE LIVER OF RATS

Carcinogenic trans-4-dimethylaminostilubene (trans-DAS) and trans-4-acetylaminostilbene (trans-AAS) as well as inactive cis-DAS and D ABB were highly and specifically labeled with tritium and administered orally to female Wistar rats. Covalent binding to liver rRNA and DNA was measured and found to be higher for the carcinogenic compounds. Digests from these nucleic acids were chromatographed on Sephadex LH-20 and 16 different nucleoside adducts were characterised by their retention volumes. Labeled trans-DAS was administered in doses ranging from 0.025-250 μ mol/kg. Binding to nucleic acids was directly proportional to the dose at low doses (0.025-2.5 μ mol/kg) and less than proportional at higher doses (25-250 μ mol/kg). The pattern of nucleoside adducts remained practically constant over the wide range of doses. A pharmacokinetically determined threshold of metabolic activation thus could not be demonstrated for this compound. A modified procedure is described to simultaneously isolate pure liver rRNA and DNA from nonfasted rats in high yields. © 1979.