Toxicity of 2-acetylaminofluorene and its metabolites in liver slices
Jackson, CD; Irving, CC
HERO ID
2147650
Reference Type
Journal Article
Subtype
Abstract
Year
1974
Language
English
| HERO ID | 2147650 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 1974 |
| Title | Toxicity of 2-acetylaminofluorene and its metabolites in liver slices |
| Authors | Jackson, CD; Irving, CC |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 29 |
| Issue | 1 |
| Page Numbers | 107-108 |
| Abstract | 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.) |
| Wosid | WOS:A1974T653800090 |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Washington, D.C. |
| Conference Name | Thirteenth Annual Meeting of the Society of Toxicology |
| Conference Date | March 10–14, 1974 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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