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Persistent Binding of 2-Acetylaminofluorene to Rat Liver DNA in Vivo and Consideration of the Mechanism of Binding of N-Hydroxy-2-acetylaminofluorene to Rat Liver Nucleic Acids¹

Veterans Administration Hospital and Department of Biochemistry, University of Tennessee, Memphis, Tennessee 38104

Previous reports that radioactivity was bound to rat liver DNA in vivo after administration of 2-acetylaminofluorene (AAF)-9-¹⁴C were confirmed. In addition, administration of several other AAF derivatives, namely N-hydroxy-AAF-9-¹⁴C, N-acetoxy-AAF-9¹⁴C, and the glucuronide of N-hydroxy-AAF-9-¹⁴C, led to the binding of higher levels of radioactivity to rat liver ribosomal RNA and DNA.

Maximum levels of bound radioactivity were found in rat liver RNA and DNA at 12–16 hr after a single injection of AAF-9-¹⁴C. Bound radioactivity disappeared rapidly from liver RNA, with approximately 3 days being required for one-half of the bound radioactivity to disappear. By four weeks after a single injection of AAF-9-¹⁴C, rat liver RNA no longer contained detectable radioactivity. On the other hand there was persistent binding of radioactivity to rat liver DNA following a single injection of AAF-9-¹⁴C. Approximately 10% of the bound radioactivity found at 12–16 hr remained associated with the DNA at 4–8 weeks after injection of AAF-9-¹⁴C.

There appeared to be at least two different mechanisms involved in the binding of N-hydroxy-AAF to rat liver ribosomal RNA and DNA in vivo since approximately 75% of the fluorene residues bound to ribosomal RNA after injection of N-hydroxy-AAF retained the N-acetyl group while the N-acetyl group was retained in only 35% of the fluorene residue bound to DNA.

¹ This investigation was supported in part by USPHS Research Grant CA-05490 from the National Cancer Institute.

Received 1/20/69. Accepted 6/13/69.