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© 1989 Oxford University Press

other

DNA adduct formation and removal in specific liver cell populations during chronic dietary administration of 2-acetylaminofluorene

Miriam c. Poirier  3, Frederick A. Beland 1, Frank H. Deal 2 and James A. Swenberg 2

1Division of Biochemical Toxicology, National Center for Toxicological Research Jefferson, AR 72079
2Department of Biochemical Toxicology and Pathobiology, Chemical Industry Institute of Toxicology Research Triangle Park, NC 27709, USA
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute Bethesda, MD 20892

3To whom reprint requests should be addressed at: Laboratory of Cellular Carcinogenesis and Tumor Promotion, Building 37, Room 3B25, NCI, NIH, Bethesda, MD 20892, USA

The concentration of DNA adducts in specific hepatic cell types has been determined in F344 rats fed 0.02% 2-acetyl-aminofluorene (AAF) for 28 days followed by control diet for an additional 28 days. In animals killed at 28 days of AAF feeding, the major DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene, was present in each cell type in the order: hepatocytes (282± 28 fmol/µg DNA) > whole liver (232 ± 33 fmol/µg DNA) > nonparenchymal cells (128 ± 30 fmol/µg DNA) > bile duct fraction (60± 12 fmol/µg DNA). After an additional 28 days on control diet, the adduct level in each cell fraction was 30–40 fmol/µg DNA. Adduct removal was biphasic in whole liver, hepatocytes and nonparenchymal cells, with a fast phase apparent until the adduct concentration reached ~60 fmol/µg DNA. In whole liver and hepatocytes this level was obtained in approximately seven days, and in nonparenchymal cells the fast phase was complete in about two days. Adduct removal in the bile duct fraction exhibited only a single slow phase. At the end of the AAF feeding, hepatocytes accounted for 86% of the total liver DNA adducts. After an additional 28 days on control diet, hepatocyte adducts still contributed a major fraction (67%) of the total persistent adduct population. Thus, hepatocytes, the target cell for AAF-induced hepatic tumors, dominate the adduct formation and removal profile observed in whole liver.


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