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 was studied in male Sprague-Dawley rats following single injections of two 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 and 29 d. Using a previously described 32P-postlabeling 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 three already known C8- and N2-acetylated and C8-deacetylated guanine derivatives and several minor unknown adducts with N-OH-AAF, a set of four new major adducts was also detected. These comprised approximately 50% of the total adducts during the first 4 h. The three 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 (greater than 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 one 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, two major and several minor adducts were detected, most of which were found to be deacetylated, and as much as 60% of the adducts measured at 24 h were still present after 9 d treatment. These data indicate that certain DNA adducts are repaired rapidly, while others persist for long periods.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010616:Phenanthrenes / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D011067:Poly dA-dT / Q000031:analogs & derivatives / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D010616:Phenanthrenes; D010761:Phosphorus Radioisotopes; D011089:Polydeoxyribonucleotides; C001366:N-hydroxy-2-acetylaminophenanthrene; D011067:Poly dA-dT; C019530:poly(dC-dG); C001365:N-hydroxy-4-acetylaminobiphenyl; D006881:Hydroxyacetylaminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene