Disease relevance of Hydroxyacetylaminofluorene

• The Salmonella mutagenesis test system was used to evaluate the in vitro mutagenic potency of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) mediated by liver and kidney subcellular fractions from X/Gf mice, a strain resistant to 2-FAA carcinogenesis [1].
• In the same cell culture assays, all four pretreatments similarly reduced cytocidal toxicity of N-hydroxy-N-2-fluorenylacetamide (0.32-32 microM; CAS: 53-95-2) [2].
• Steroid hormone receptors in the rat mammary adenocarcinoma induced by N-hydroxy-N-2-fluorenylacetamide [3].
• Selective oligonucleotide hybridization demonstrated a CG----AT transversion at the first position of the 61st codon in NIH 3T3 transformants derived from 7 of 7 N-hydroxy-2-acetylaminofluorene-induced hepatomas [4].
• For liver cancer induction, rats were fed 120 ppm N-hydroxy-N-2-fluorenylacetamide in the diet for 16 weeks, then were continued on control diet [5].

High impact information on Hydroxyacetylaminofluorene

• The mutagenic activations of N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) by subcellular fractions of the livers of the Sprague-Dawley rat, C57BL mouse, Hartley guinea pig, Syrian golden hamster, and Macaca fuscata fuscata monkey were examined for sensitivity to paraoxon, which inhibits a deacetylase but not an arylhydroxamic acid acyltransferase [6].
• Mutagenic activation of N-2-fluorenylacetamide and N-hydroxy-N-2-fluorenylacetamide in subcellular fractions from X/Gf mice [1].
• Mutagenic activation of N-hydroxy-2-acetylaminofluorene by developing epithelial cells of rat small intestine and effects of antioxidants [7].
• No effect was observed on the mutagenic activation of N-hydroxy-2-acetylaminofluorene by liver microsomes after MCA treatment [8].
• Nonrandom binding of the carcinogen N-hydroxy-2-acetylaminofluorene to repetitive sequences of rat liver DNA in vivo [9].

Chemical compound and disease context of Hydroxyacetylaminofluorene

• The effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic activities of the proximate carcinogen, N-hydroxy-2-acetylaminofluorene, and the ultimate carcinogen, N-acetoxy-2-acetylaminofluorene, was examined by estimating the frequency of his+ revertants of Salmonella typhimurium [10].
• Metabolic activation and genotoxicity of N-hydroxy-2-acetylaminofluorene and N-hydroxyphenacetin derivatives in Reuber (H4-II-E) hepatoma cells [11].
• As compared to their normal male littermates, male brachymorphic B6C3F2 mice, which are deficient in hepatic 3'-phosphoadenosine-5'-phosphosulfate (PAPS), treated with N-hydroxy-AAF formed only 25% as many hepatic DNA adducts and developed only 10% as many hepatomas [12].
• Comparative toxicity and mutagenicity of N-hydroxy-2-acetylaminofluorene and 7-acetyl-N-hydroxy-2-acetylaminofluorene in human lymphoblasts [13].
• Cyclic-AMP-dependent protein kinase activity was depressed in whole spleen as well as in isolated splenic lymphocytes from 3-methylcholanthrene (MCA), R3230 AdCa mammary adenocarcinoma, N-hydroxy-2-acetylaminofluorene, and 4-dimethylaminoazobenzene (DMAAB) tumor-bearing Fischer rats as compared to control animals [14].

Biological context of Hydroxyacetylaminofluorene

• It is suggested that the reported sex difference in the hepatocarcinogenicity of N-hydroxy-2-acetylaminofluorene might be peculiar to the Sprague-Dawley rat [15].
• Homodimeric and heterodimeric aryl sulfotransferases catalyze the sulfuric acid esterification of N-hydroxy-2-acetylaminofluorene [16].
• DNA repair was induced by 2-aminofluorene (2-AF) and its acetylated derivatives 2-acetyl-aminofluorene and N-hydroxy-2-acetylaminofluorene [17].
• Treatment of hepatocytes with paraoxon prior to exposure to N-hydroxy-2-acetylaminofluorene (N-OH-AAF) or N-acetoxy-2-acetylaminofluorene (N-OAc-AAF) partially inhibited both DNA damage and the bacterial mutagenicity caused by these agents [18].
• The catalytic effect of bovine serum albumin on the ortho rearrangement of the potential ultimate carcinogen, N-(sulfooxy)-2-(acetylamino)fluorene, generated enzymatically from N-hydroxy-2-(acetylamino)fluorene and evidence for substrate specificity of the enzymatic sulfonation of arylhydroxamic acids [19].

Anatomical context of Hydroxyacetylaminofluorene

• Mechanism of in vitro mutagenic activation and covalent binding of N-hydroxy-2-acetylaminofluorene in isolated liver cell nuclei from rat and mouse [20].
• In addition to short chain acyl coenzyme As, N-hydroxy-2-acetylaminofluorene also served as an acetyl donor for the activation of N-OH-Glu-P-1 and N-OH-Trp-P-2 in liver cytosol systems [21].
• Peroxidative metabolism of a carcinogen, N-hydroxy-N-2-fluorenylacetamide, by rat uterus and mammary gland in vitro [22].
• Biochemical and morphological changes in hepatic nuclear membranes produced by N-hydroxy-2-acetylaminofluorene [23].
• The effect of N-hydroxy-2-acetylaminofluorene on the ultrastructure and synthesis of hepatic neclear membranes was evaluated in partially hepatectomized rats [23].

Associations of Hydroxyacetylaminofluorene with other chemical compounds

• Incubation of the carcinogenic arylhydroxamic acids N-hydroxy-N-2-fluorenylacetamide or N-hydroxy-N-4-biphenylacetamide and tRNA with 105,000 times g supernatants of homogenates of human small intestine, liver, or colon led to formation of arylamine-substituted nucleic acid adducts [24].
• Covalent binding of 2-acetylaminofluorene, 2-aminofluorene, and N-hydroxy-2-acetylaminofluorene to rat liver nuclear DNA and protein in vivo and in vitro [25].
• In addition, we found that N-nitrosodiethylamine, 4-aminoazobenzene, and N-hydroxy-2-acetylaminofluorene all caused G to T transversions in the N-ras gene (codons 12 or 13) [26].
• Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of the carcinogen N-hydroxy-N-acetyl-2-aminofluorene as effected by cyanide and ascorbate [27].
• Immunosuppression in primary liver and colon tumor induction with N-hydroxy-N-2-fluorenylacetamide and azoxymethane [5].

Gene context of Hydroxyacetylaminofluorene

• We previously established that inactivation of hamster NAT1 by N-hydroxy-2-acetylaminofluorene is the result of sulfinamide adduct formation with Cys68 [28].
• SULT1C1, which can catalyze the sulfation of N-hydroxy-2-acetylaminofluorene, was expressed in Caco-2, BeWo and KB562 [29].
• The spectra of ras gene mutations in liver tumors that were induced by 15 daily i.p. injections of 7,12-dimethylbenz[a]anthracene (DMBA), 4-aminoazobenzene (AAB), N-hydroxy-2-acetylaminofluorene (N-OH-AAF) or N-nitrosodiethylamine (DEN) were compared to those previously obtained for tumors induced by a single but higher dose of each carcinogen [30].
• Metabolic activation of N-hydroxy-2-acetylaminofluorene by NAT1 and NAT2 was partially sensitive to 100 microM paraoxon [31].
• Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene [32].

Analytical, diagnostic and therapeutic context of Hydroxyacetylaminofluorene

• The capacity for in vitro sulfation of N-hydroxy-2-acetylaminofluorene in the postmicrosomal supernatant, markedly sex differentiated in the rat (male greater than female), was completely feminized by neonatal but not by adult castration [33].
• Spin trapping of the primary radical involved in the activation of the carcinogen N-hydroxy-2-acetylaminofluorene by cumene hydroperoxide-hematin [34].
• N-Hydroxy-2-acetylaminofluorene (N-OH-AAF) was administered i.p. to male Wistar rats 17 h after partial hepatectomy [35].
• The in vitro metabolism of a locally carcinogenic N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) by rat peritoneal polymorphonuclear leukocytes (PMNL), chiefly neutrophils, elicited with intraperitoneal injections of proteose peptone, was examined [36].
• The O-acetates of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-acetyl-4-aminobiphenyl induced chromosomal aberrations in a population of cells samples at 22--25 h after treatment [37].

References