Formation and persistence of DNA adducts during and after a long-term administration of 2-nitrofluorene

2-Nitrofluorene (NF) is an environmental pollutant, Our previous studies ha ve shown that NF is a carcinogen, primarily targeting the liver, kidney and forestomach in rats. NF-induced DNA adducts were also shown higher levels in the tumor-targeting tissues compared to non-tumor targeting organs. The present study was aimed to observe the kinetics of DNA adduct formation and persistence during the process of NF induced tumor formation. NF was suppl emented in diet at three dose levels and was fed to rats continuously for u p to 11 months. DNA adduct formation in the liver, kidney, spleen and stoma ch of rats after different period (10 days and 11 months) of NF administrat ion was analyzed with P-32-HPLC techniques. DNA adduct persistence in the l iver was also assessed after the withdrawal of NF administration. Four majo r NF-DNA adducts (adducts A, B, C and D) were found in the liver and kidney . DNA adduct D showed high level in the forestomach mucosa after 10 days of NF feeding while adducts A and C were undetectable. DNA adduct C and D co- migrated with C3-(deoxyguanosin-N-2-yl)-2-acetylaminofluorene (dG-N-2-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), respectively, by P-3 2-HPLC co-chromatography. DNA adducts A and B constituted the major part (> 80%) of NF-DNA adducts after a long period (11 months) of NF feeding. The four NF-DNA adducts showed different recovery from different enrichment pro cedures, i.e., nuclease PI or butanol treatment. Three out of the four NF-D NA adducts were still detectable in the rat liver after 11 months on the ba sal diet. In conclusion, four major DNA adducts are induced by NF oral admi nistration. Among those, one is identified as dG-N-2-AAF and another one as dG-C8-AF. The four NF-DNA adducts showed different kinetics of formation a nd persistence, which may play different roles in NF-induced tumor formatio n. (C) 1999 Elsevier Science B.V. All rights reserved.