Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and, 2-acetylaminophenanthrene
Formation and removal of hepatic DNA adducts were studied in male Sprague-Dawley rats following single injections of 2 hepatocarcinogens (N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP)) and a nonhepatocarcinogen (N-hydroxy-2-acetylaminophenanthrene (N-OH-AAP)) at 0.5 h, 1.5 h, 4 h, 24 h, 9 d [day] and 29 d. Using a previously described 32P-post-labeling assay, maximal DNA binding of these compounds was observed at approximately 1.5 h, 0.5 h and 24 h, respectively. In addition to the formation of 3 already known C8- and N2-acetylated and C8-deacetylated guanine derivatives and several minor unknown adducts with N-OH-AAF, a set of 4 new major adducts was also detected. These comprised .apprx. 50% of the total adducts during the first 4 h. The 3 known adducts amounted to 58, 16 and 6% of the 1.5-h value after 24 h, 9 d and 29 d, respectively, while the bulk (> 84%) of the new major adducts were removed from the DNA within 24 h and found only in traces after 9 d. N-OH-AABP formed several unknown minor adducts, in addition to the 1 major C8-deacetylated and two minor C8- and N2-acetylated guanine derivatives; only the C8-deacetylated and N2-acetylated adducts were detected after 29 d. In the case of N-OH-AAP, 2 major and several minor adducts were detected, most of which were deacetylated, and as much as 60% of the adducts measured at 24 h were still present after 9 d treatment. Certain DNA adducts are repaired rapidly, while others persist for long periods.