Health & Environmental Research Online (HERO)


Print Feedback Export to File
2147650 
Journal Article 
Abstract 
Toxicity of 2-acetylaminofluorene and its metabolites in liver slices 
Jackson, CD; Irving, CC 
1974 
1 
Toxicology and Applied Pharmacology
ISSN: 0041-008X
EISSN: 1096-0333 
HEEP/75/07651 
29 
1 
107-108 
English 
WOS:A1974T653800090 
is part of a larger document 3378179 Abstracts of papers for the Thirteenth Annual Meeting of the Society of Toxicology, Washington, D.C. March 10–14, 1974
Rat liver slices were investigated as a possible in vitro system for studying the initial effects of a hepatocarcinogen on liver cells. Binding of N-hydroxy-2-acetylaminofluorene (N-HOAAF) to RNA and DNA ofliver slices from male Holtzmann rats was 5- to 6-fold greater than that of females. Inhibition of RNA and protein synthesis by N-HO-AAF was 2-3 times greater in liver slices from male rats compared to females. The glucuronide conjugate of N-HO-AAF (N-GlO-AAF) was half as effective in inhibiting RNA synthesis as N-HO-AAF. 2-Acetylaminofluorene (AAF) had little or no effect on RNA synthesis in liver slices. Although 0.2 mM N-HO-AAF reduced both RNA and protein synthesis in slices 80%, there was no inhibition of DNA synthesis with the concentrations studied (0.05-0.8 mM). Inhibition of RNA synthesis in liver slices by several N-hydroxy-N-arylacetamides (0.2 mM) was found to be as follows: N-hydroxy-2-acetylaminofluorene, 80.3%; N-hydroxy-2- acetylaminophenanthrene, 54.4% ; N-hydroxy-4-acetylaminostilbene, 37.9%; N-hydroxy-4-acetylaminobiphenyl, 35.3%. These results indicate that the effect of AAF and its metabolites on rat liver slices in vitro is similar to that observed in vivo and that the glucuronide conjugate may contribute significantly to the hepatotoxicity observed in vivo during oral administration of AAF. The results also indicate that the metabolism and/or reactivity of the N-hydroxy-N-arylacetamides is highly dependent on the structure of the aryl substituent. (Supported by Veterans Administration Research Funds.) 
Thirteenth Annual Meeting of the Society of Toxicology 
Washington, D.C. 
March 10–14, 1974