REACTION OF GLUCURONIDE OF CARCINOGEN N-HYDROXY-2-ACETYLAMINOFLUORENE WITH NUCLEIC ACIDS

The interaction of the glucuronide of the carcinogen N-hydroxy-2-acetylaminofluorene with nucleic acids in vitro has been studied. Sodium (N-acetyl-N-2-[9-14C]-fluorenylhydroxylamine β-d-glucosid)uronate was incubated with yeast tRNA, rat liver rRNA or with calf thymus DNA and the nucleic acids were recovered from the reaction mixture and purified to a constant specific radioactivity. At pH 8 (37°) the degree of binding of radioactivity was linear with time, amounting in 24 h to 4-8 mμmoles per mg of nucleic acid when 0.6 μmole of the glucuronide was incubated with 2 mg of nucleic acid. The reaction of the glucuronide with RNA or DNA was pH-dependent, with a higher rate of reaction occurring as the pH increased. Comparative studies on the binding of radioactivity to rat liver rRNA and DNA in vivo showed that more radioactivity was bound to these nucleic acids after the administration of sodium (N-acetyl-N-2-[9-14C]fluorenylhydroxylamine β-d-glucosid)uronate than after giving 2-acetylamino[9-14C]fluorene, but less than was obtained after injection of N-hydroxy-2-acetylamino[9-14C]fluorene. The results of these studies were interpreted to indicate that the glucuronide of N-hydroxy-2-acetylaminofluorene, a known metabolite of the carcinogens 2-acetylaminofluorene and N-hydroxy-2-acetylaminofluorene, might account in part for the observed binding of these carcinogens to liver nucleic acids in vivo. © 1969.