2-acetylaminofluorene

2-アセチルアミノフルオレン

関

2-AAF、acetylaminofluorene

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/15 08:21:22」(JST)

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2-Acetylaminofluorene

Names
Systematic IUPAC name N-(9H-fluoren-2-yl)acetamide
Other names 2-Acetaminofluorene N-2-Fluorenylacetamide N-Acetyl-2-aminofluorene
Identifiers
CAS Number	53-96-3 Y
Abbreviations	2-AAF
Beilstein Reference	2807677
ChEBI	CHEBI:17356 Y
ChEMBL	ChEMBL311469 Y
ChemSpider	5686 Y
EC Number	200-188-6
InChI InChI=1S/C15H13NO/c1-10(17)16-13-6-7-15-12(9-13)8-11-4-2-3-5-14(11)15/h2-7,9H,8H2,1H3,(H,16,17) Y Key: CZIHNRWJTSTCEX-UHFFFAOYSA-N Y InChI=1/C15H13NO/c1-10(17)16-13-6-7-15-12(9-13)8-11-4-2-3-5-14(11)15/h2-7,9H,8H2,1H3,(H,16,17) Key: CZIHNRWJTSTCEX-UHFFFAOYAF
Jmol interactive 3D	Image Image
KEGG	C02778 Y
MeSH	2-Acetylaminofluorene
PubChem	5897
RTECS number	AB9450000
SMILES CC(=O)Nc1ccc2c(Cc3ccccc23)c1 CC(=O)NC1=CC=C2C(CC3=C2C=CC=C3)=C1
UN number	3077
Properties
Chemical formula	C15H13NO
Molar mass	223.28 g·mol−1
Appearance	Vivid, light brown, opaque crystals
Melting point	192 to 196 °C (378 to 385 °F; 465 to 469 K)
log P	3.264
Hazards
Main hazards	potential occupational carcinogen
GHS pictograms
GHS signal word	Danger
GHS hazard statements	H302, H350
GHS precautionary statements	P201, P308+313
EU classification (DSD)	T N
R-phrases	R45, R22, R51/53
S-phrases	S53, S36/37/39, S45
US health exposure limits (NIOSH):
PEL (Permissible)	[OSHA-Regulated Carcinogen]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

2-Acetylaminofluorene (AAF, 2-AAF) is a carcinogenic and mutagenic derivative of fluorene. It is used as a biochemical tool in the study of carcinogenesis. It induces tumors in a number of species in the liver, bladder and kidney. The metabolism of this compound in the body by means of biotransformation reactions is the key to its carcinogenicity. 2-AAF is a substrate for cytochrome P-450 (CYP) enzyme, which is a part of a super family found in almost all organisms. This reaction results in the formation of N-hydroxy-2-acetylaminofluorene which is a proximal carcinogen and is more potent than the parent molecule. The N-hydroxy metabolite undergoes several enzymatic and non-enzymatic rearrangements. It can be O-acetylated by cytosolic N-acetyltransferase enzyme to yield N-acetyl-N-acetoxyaminofluorene. This intermediate can spontaneously rearrange to form the arylamidonium ion and a carbonium ion which can interact directly with DNA to produce DNA adducts. In addition to esterification by acetylation, the N-hydroxy derivative can be O-sulfated by cytosolic sulfur transferase enzyme giving rise to the N-acetyl-N-sulfoxy product.

In addition, the cytosolic N,O-aryl hydroxamic acid acyltransferase enzyme catalyzes the transfer of the acetyl group from the N atom of the N-OH-2-AAF to the O atom of the N-OH group to produce N-acetoxy-2-aminofluorene (N-OH-2-AF). This reactive metabolite spontaneously decomposes to form a nitrenium ion which will also react with DNA. However, the product of this latter reaction is the deacetylated aminofluorene adduct. The interconversion of amide and amine metabolites of 2-AAF can further occur via the microsomal enzyme deacetylase producing the N-hydroxy metabolite of the amine derivative. Subsequent esterification of the aryl hydroxylamine by sulfur transferase yields the sulfate ester which also spontaneously decompose to form nitrenium ion. The reactive nitrenium, carbonium and arylamidonium ion metabolites of 2-AAF react with the nucleophilic groups in DNA, proteins and endogenous thiols like glutathione. Other metabolites such as the N,O-glucuronide, although not directly activated products, can be important in the carcinogenic process because they are capable of degradation to proximal N-hydroxy metabolites. This metabolite is presumed to be involved in formation of bladder tumors. The mechanism for this is thought to involve degradation of glucuronide in the bladder due to acidic pH of urine.

See also

• Acetoxyacetylaminofluorene
• Hydroxyacetylaminofluorene

References

English Journal

• Chemoprotective effect of Vernonia amygdalina Del. (Astereacea) against 2-acetylaminofluorene-induced hepatotoxicity in rats.

• Adesanoye OA1, Adekunle AE1, Adewale OB1, Mbagwu AE1, Delima AA1, Adefegha SA1, Molehin OR1, Farombi EO2.
• Toxicology and industrial health.Toxicol Ind Health.2016 Jan;32(1):47-58. doi: 10.1177/0748233713498436. Epub 2013 Sep 10.
• Natural products possessing antioxidant properties play a very crucial role in ameliorating deleterious effects of reactive oxygen species. This study investigated the chemoprotective properties of methanolic extract of Vernonia amygdalina (MEVA) in an experimental model of hepatic oxidative damage
• PMID 24021430

• Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis.

• Hung TM1, Yuan RH2, Huang WP3, Chen YH4, Lin YC5, Lin CW6, Lai HS7, Lee PH8.
• The American journal of pathology.Am J Pathol.2015 Sep;185(9):2454-67. doi: 10.1016/j.ajpath.2015.05.010. Epub 2015 Jul 7.
• Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic liv
• PMID 26158232

• Nrf2, but not β-catenin, mutation represents an early event in rat hepatocarcinogenesis.

• Zavattari P1, Perra A1, Menegon S2, Kowalik MA1, Petrelli A2, Angioni MM1, Follenzi A3, Quagliata L4, Ledda-Columbano GM1, Terracciano L4, Giordano S2, Columbano A1.
• Hepatology (Baltimore, Md.).Hepatology.2015 Sep;62(3):851-62. doi: 10.1002/hep.27790. Epub 2015 Apr 22.
• Hepatocellular carcinoma (HCC) develops through a multistage process, but the nature of the molecular changes associated with the different steps, the very early ones in particular, is largely unknown. Recently, dysregulation of the NRF2/KEAP1 pathway and mutations of these genes have been observed
• PMID 25783764

Japanese Journal

• Detection of Initiation Activity of 1,2-Dimethylhydrazine in in vivo Medium-Term Liver Initiation Assay System using 4-Week-Old Rats without Hepatocellular Proliferative Stimuli during the Test Chemical Treatment Period

• ASAOKA Yoshiji,SAKAI Hiroki,HIRATA Akihiro,SASAKI Jun,GORYO Masanobu,MIYAMOTO Yohei,YANAI Tokuma,MASEGI Toshiaki,OKADA Kosuke
• Journal of Veterinary Medical Science 72(1), 43-53, 2010
• … Next, the in vivo medium-term liver initiation assay model using 4-week-old rats without cell proliferation stimuli was evaluated for the detection of the initiation activity of 1,2-dimethylhydrazine (DMH), which is a well-known genotoxic carcinogen. … subsequently, these rats were treated promotion treatment consisted of administration of 2-acetylaminofluorene and carbon tetrachloride. …
• NAID 130000134508

• Extrapolation of the Animal Carcinogenesis Threshold to Humans

• Nagao Minako,Ishikawa Satoko,Nakagama Hitoshi,Watanabe Masahiko
• Genes and environment : the official journal of the Japanese Environmental Mutagen Society 30(4), 160-165, 2008-11-20
• … The ED01 study of 2-acetylaminofluorene, performed in the U.S. using more than 24,000 mice, provides us with information about the practical limits of an attainable experimental approach for determining carcinogenesis thresholds. … Despite smaller study sizes, we attempted to evaluate the carcinogenesis dose response to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) in rats, using published data. …
• NAID 110007007990

Related Links

• 2-Acetylaminofluorene | Technology Transfer Network Air ...

Hazard Summary 2-Acetylaminofluorene is used by scientists to study the carcinogenicity and mutagenicity of aromatic amines. No information is available on the acute (short-term), chronic (long-term), reproductive, or ...

• 2-Acetylaminofluorene - Centers for Disease Control and ...

2-Acetylaminofluorene Synonyms & Trade Names AAF, 2-AAF, 2-Acetaminofluorene, N-Acetyl-2-aminofluorene, FAA, 2-FAA, 2-Fluorenylacetamide CAS No. 53-96-3

Related Pictures

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★リンクテーブル★

リンク元	「N-2-フルオレニルアセタミド」「2-AAF」「2-アセチルアミノフルオレン」
関連記事	「acetylaminofluorene」

「N-2-フルオレニルアセタミド」

　　[★]

英

N-2-fluorenylacetamide

同

2-アセチルアミノフルオレン 2-acetylaminofluorene 2-AAF

「2-AAF」

　　[★]

• 2-アセチルアミノフルオレン

関

2-acetylaminofluorene、acetylaminofluorene

「2-アセチルアミノフルオレン」

　　[★]

英

2-acetylaminofluorene、2-AAF

関

アセチルアミノフルオレン

「acetylaminofluorene」

　　[★]

アセチルアミノフルオレン

関

2-AAF、2-acetylaminofluorene