Disease relevance of Aminofluoren

• Cultured tobacco plant cells activated 2-aminofluorene to an agent mutagenic to Salmonella typhimurium strain TA98 [1].
• In contrast to these results, hepatocytes from rapid acetylators were more sensitive than those from slow acetylators to toxicity from the carcinogen 2-aminofluorene and displayed greater amounts of DNA repair [2].
• The Escherichia coli genome contains a C-G1-G2-C-G3-C-C NarI hot spot sequence for -2 deletion mutations at G3 by aromatic amine carcinogens 2-acetylaminofluorene (AAF) and 2-aminofluorene (AF) that form covalent adducts at the C8-position of the guanine ring [3].
• Large-scale conformational searches with potential energy minimization, using the torsion angle space molecular mechanics program DUPLEX, were employed to explore the conformation of all 16 deoxydinucleoside monophosphates bearing 2-aminofluorene (AF) or 2-(acetylamino)fluorene (AAF) modification on guanine [4].
• Pretreatment of mouse embryo fibroblasts with several chemicals, including 7,12-dimethylbenz-(a)-anthracene, 2-aminofluorene, aflatoxin B1, benzo-(a)-pyrene, styrene oxide, and the No. 4 fraction of tobacco smoke condensate, resulted in severely reduced production of interferon when the cells were challenged with Newcastle disease virus [5].

Psychiatry related information on Aminofluoren

• Studies of genetically determined differences in arylamine acetylation with the model carcinogen 2-aminofluorene in C57BL/6J and A/J inbred mouse strains showed that individual differences in the pharmacokinetics of 2-aminofluorene were dependent on differences in 2-aminofluorene N-acetyltransferase activity in liver and blood [6].
• 2-Aminofluorene was activated by four PB-inducible preparations (PB-Ia, Ic, Id, and IIa), but only moderately [7].

High impact information on Aminofluoren

• Crystal structures of 2-acetylaminofluorene and 2-aminofluorene in complex with T7 DNA polymerase reveal mechanisms of mutagenesis [8].
• The second form of the modified oligomer duplex may be representative of a pre-mutagenic conformation in that the 2-aminofluorene moiety is stacked within the DNA helix, disrupting base pairing between the 2-aminofluorene-modified guanine and its complementary cytosine [9].
• One- and two-dimensional NMR shows that the carcinogen 2-aminofluorene exists in two unique, interchangeable conformations when covalently bound to a model human c-H-ras1 proto-oncogene codon 61 oligomer duplex [9].
• Unique N-acetyl-2-aminofluorene (AAF) or 2-aminofluorene (AF) adducts were introduced into the Xenopus borealis somatic 5S RNA gene between the intragenic control region and the transcription termination site [10].
• Relationship between the genetically determined acetylator phenotype and DNA damage induced by hydralazine and 2-aminofluorene in cultured rabbit hepatocytes [2].

Chemical compound and disease context of Aminofluoren

• The rabbit pulmonary and hepatic microsomal pathways for the metabolism of 2-acetylaminofluorene (AAF) and 2-aminofluorene (AF) to mutagenic products were investigated by means of high performance liquid chromatography and the Salmonella mutagenicity assay [11].
• Arylamine N-acetyltransferase (NAT) activities with p-aminobenzoic acid (PABA) and 2-aminofluorene (AF) were determined in H. pylori collected from peptic ulcer patients [12].
• The mutagenicities of 6-aminobenzo[a]pyrene (6-NH2-BP), 4-, 11- and 12-NH2-BP, and two N,N-diacetyl derivatives (4- and 12-N(Ac)2-BP) were compared to that of the present compound, BP, and to the aromatic amine, 2-aminofluorene (AF), in the Ames' Salmonella typhimurium assay [13].
• Alkyl-substituted derivatives of 2-aminonaphthalene (2-AN) 1, 2-aminofluorene (2-AF) 6 and 4-aminobiphenyl (4-ABP) 11 were synthesized and the mutagenic activity of these compounds determined in Salmonella typhimurium strains TA98 and TA100 with and without S9 mix [14].
• Antimutagenesis was assayed against the mutagenic activity of m-phenylenediamine (m-PDA), 2-aminofluorene (2-AF), 1-aminopyrene (1-AP), 2-aminoanthracene (2-AA) and 9-aminophenantrene (9-AP) in Salmonella typhimurium (S. typhimurium) YG1024, in different co-treatment approaches [15].

Biological context of Aminofluoren

• Acetylation of 2-aminofluorene in the presence of ethyl acetate (and deacetylation of 2-acetylaminofluorene) mediated by an enzyme sensitive to inhibition by either paraoxon or sodium fluoride was also observed [16].
• Isolated parenchymal cells of rat liver have been used in a study of the metabolic activation of derivatives of the carcinogens 4-aminobiphenyl and 2-aminofluorene [17].
• The levels of both 2-aminofluorene (AF) N-acetyltransferase and N-OH-AF O-acetyltransferase activity reflected the N-acetylator genotype in liver, intestine, kidney and lung cytosols [18].
• 2-Nitrofluorene and 2-aminofluorene induced umuC gene expression more strongly in the NM6001 strain than in the NM6002 strain [19].
• Urinary bladder possessed N-acetyltransferase activity for both 2-aminofluorene and p-aminobenzoic acid which differed 2-fold, and reflected the liver and blood phenotype [20].

Anatomical context of Aminofluoren

• Human colon cytosols from 48 fresh surgical samples were investigated for NAT activity toward p-aminobenzoic acid and the arylamine carcinogens 4-aminobiphenyl, 2-aminofluorene, and beta-naphthylamine [21].
• The soluble protein fraction (without added microsomes) did not activate 2-aminofluorene for bacterial mutagenesis [22].
• Bacterial mutagenesis from 2-aminofluorene mediated by washed rat liver microsomes was elevated 2- to 3-fold by addition of the hepatic soluble protein fraction [22].
• Prostaglandin H synthase in the presence of arachidonic acid catalyzes the peroxidative metabolism of 2-aminofluorene (2-AF) to an electrophile(s) which binds covalently to calf thymus DNA in vitro [23].
• The cytochrome P-450 monooxygenase system of rabbit bladder mucosa: enzyme components and isozyme 5-dependent metabolism of 2-aminofluorene [16].

Associations of Aminofluoren with other chemical compounds

• The N-hydroxy, N-hydroxy-N-acetyl, N-hydroxy-N-glucuronosyl derivatives of 2-aminofluorene (2-AF) and 4-aminobiphenyl (4-ABP) induced UDS in primary cultures of rat mammary epithelial cells, but 2-AF, the O-glucuronide of N-hydroxy-N-acetyl-2-AF (N-OH-AAF) and 4-ABP did not [24].
• Addition of microsomes increased the mutagenicity of AAF, but not that of 2-aminofluorene or 2,4-diaminoanisole, presumably by deacetylation of N-hydroxy-2-acetylaminofluorene to N-hydroxy-2-aminofluorene [25].
• In this study, we examined the in vitro hepatic metabolism of the carcinogens, 2-aminofluorene (2-AF) and 2-naphthylamine (2-NA), and the suspected carcinogen, 1-naphthylamine (1-NA), using high-pressure liquid chromatography [26].
• Kinetic constants determined for the expressed enzymes with 2-aminofluorene and p-aminobenzoic acid indicated that Km values were not significantly different between the enzymes, although the Vmax value of NAT-2(99asn) was consistently 2-3-fold higher than that of NAT-1 or NAT-2(99ile) [27].
• In the present study, we found that dog liver microsomes were capable of N-acetylation of 2-aminofluorene and N,O-acetyltransfer of N-hydroxy-2-acetylaminofluorene (N-OH-AAF), and that these activities were inhibited by paraoxon [28].

Gene context of Aminofluoren

• Interestingly, the carcinogen 2-aminofluorene was very efficiently metabolized by both NAT1 and NAT2 [29].
• All rabbit gastrointestinal tissues other than stomach possess a high capacity for the activation of 2-aminofluorene compatible with CYP4B1 expression [30].
• In control yeast, no induction of RNR3 was observed upon exposure to 2-aminofluorene or aflatoxin B1 [31].
• Genotoxic activation of 2-aminofluorene (a marker for Cyp4b1) by male and female mouse kidney microsomes were not affected by the SCD phenotype [32].
• CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S9 fractions also [33].

Analytical, diagnostic and therapeutic context of Aminofluoren

• Finally, we used HPLC to determine the ratio of acetylated (12%) to deacetylated (88%) 2-aminofluorene adducts formed in the parental cells [34].
• Activation of the procarcinogens benzo(a)pyrene and 2-fluorenamine by liver homogenates (S9) prepared from senescent male CFN rats and C57BL/6J mice resulted in an enhanced production of mutagenic metabolites when compared to young rodents, as indicated by an enhancement of the induced reversion frequency in a Salmonella typhimurium bioassay [35].
• The presence of homologues of rabbit cytochrome P-450 isozyme 5 in pulmonary and hepatic microsomal preparations from guinea pig, mouse, monkey, hamster, and rat was examined by immunoblotting and inhibition of metabolism of 2-aminofluorene with antibodies to isozyme 5 [36].
• Metabolism of 2-aminofluorene was measured both colorimetrically (formation of a reduced iron chelate from the N-hydroxyfluorene metabolite) and radiochemically (separation of 3H-metabolites by high performance liquid chromatography and quantitation by scintillation counting) [36].
• The influence of partial hepatectomy on the level of 2-aminofluorene (2-AF) induced DNA adducts in rat liver was studied [37].

References