DNA adduct formation and removal in specific liver cell populations during chronic dietary administration of 2-acetylaminofluorene.
The concentration of DNA adducts in specific hepatic cell types has been determined in F344 rats fed 0.02% 2-acetylaminofluorene (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/micrograms DNA) greater than whole liver (232 +/- 33 fmol/micrograms DNA) greater than nonparenchymal cells (128 +/- 30 fmol/micrograms DNA) greater than bile duct fraction (60 +/- 12 fmol/micrograms DNA). After an additional 28 days on control diet, the adduct level in each cell fraction was 30-40 fmol/micrograms DNA. Adduct removal was biphasic in whole liver, hepatocytes and nonparenchymal cells, with a fast phase apparent until the adduct concentration reached approximately 60 fmol/micrograms 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.
Poirier
M C
MC
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892.
Beland
F A
FA
Deal
F H
FH
Swenberg
J A
JA
D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D001652:Bile Ducts / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004032:Diet; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D004247:DNA; D015073:2-Acetylaminofluorene