Partial persistency of 2-aminofluorene and N-acetyl-2-aminofluorene in rat liver DNA

Abstract

Male rats were treated with [ring-³H]N-acetyl-2-aminofluorene and sacrificed at different periods of time after a single i.p. dose. Chromatin was isolated from liver homogenates and treated with RNAse and proteinase K. The resulting crude DNA was purified as the N-hexadecyl-N-trimethylammonium salt. The amounts of 2-aminofluorene and N-acetyl-2-aminofluorene bound to carbon-8 of guanine were determined in the DNA via acid hydrolysis and high pressure liquid chromatography of the hydrolysate. These two major interaction products of the carcinogen decreased rapidly during the first 2 weeks but in the second 2 weeks the decrease of both interactions was much smaller and approximately 15% of the amount that was bound after 24 h remained persistently bound to the DNA. Differences in liver DNA binding after 24 h were observed between male rats of the strain R-Amsterdam (Wistar-related) and Sprague Dawley males. At equal dose levels of N-acetyl-2-aminofluorene, liver DNA of Sprague Dawley rats contained 1/3 of the amount of N-(guanin-8-yl)-2-aminofluorene and 1/2 of the amount of N-(guanin-8-yl)-N-acetyl-2-aminofluorene present in liver DNA of the R-Amsterdam strain.