Disease relevance of aniline

• Bacterial luciferase and NAD(P)H: FMN oxidoreductase isolated from Beneckea harveyi were covalently linked via diazotization to arylamine porous glass beads which had been cemented onto plain glass rods [1].
• We examined arylamine substrate and acetyl coenzyme A cofactor affinities, and the N-acetyltransferase catalytic activities of the wild-type and 14 different mutant or chimeric human NAT2 alleles expressed in an Escherichia coli JM105 expression system [2].
• Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: metabolism and mutagenic activation of aromatic amines [3].
• Acetylator genotype-dependent expression by the human colon of arylamine N-acetylation capacity, catalyzed by acetyl coenzyme A-dependent N-acetyltransferase(s) (EC 2.3.1.5) (NAT), may be an important risk factor in the initiation of colorectal cancer [4].
• In aromatic amine-induced rat hepatomas, the aldehyde dehydrogenase (AIDH) phenotype is qualitatively and quantitatively different from that of normal liver [5].

High impact information on aniline

• The activation of these, and also some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 (P450) [6].
• These results demonstrate considerable tissue, species, and compound specificity for the metabolic activation of aromatic amines and provide further evidence in support of bladder activation as a mechanism of aromatic amine-induced bladder cancer [7].
• The aromatic amine 2,4-toluenediamine was fed at levels of 50 and 100 ppm to inbred, barrier-raised F344 rats for 2 years [8].
• Previously, we showed that NAT2 polymorphisms did not influence bladder cancer risk among Chinese workers exposed exclusively to benzidine (BZ), suggesting that NAT2 N-acetylation is not a critical detoxifying pathway for this aromatic amine [9].
• These data strongly suggest that defective arylamine N-acetylation in the rabbit model is caused by a gene deletion resulting in an absence of specific mRNA and NAT enzyme protein [10].

Chemical compound and disease context of aniline

• The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid [11].
• Several other drugs which have been implicated in drug-induced lupus also contain an aromatic amine or hydrazine group [12].
• 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a heterocyclic aromatic amine found in cooked meats and dietary exposure to PhIP has been implicated in the etiology of colon cancer in humans [13].
• Azido- and nitro-PhIP, relatives of the heterocyclic arylamine and food mutagen PhIP--mechanism of their mutagenicity in Salmonella [14].
• The aromatic amine oxidase from Escherichia coli (ECAO) utilizes Cu(II) and 2,4,5-trihydroxyphenylalanine quinone (TPQ) as cofactors in enzymatic catalysis [15].

Biological context of aniline

• The polymorphic expression of these acetylation activities may be important risk factors in human susceptibility to bladder cancer from arylamine carcinogens [16].
• Significantly greater mean apparent Vmax levels were found in colons from rapid as compared to intermediate acetylators (1.5-3-fold) (P less than 0.001) and intermediate as compared to slow (2.5-3-fold) (P less than 0.005) acetylator phenotypes for the four arylamine substrates [4].
• Aberrant crypts, the earliest morphologically evident preneoplastic lesions in chemical colon carcinogenesis, were measured in rapid and slow acetylator congenic Syrian hamsters administered 3,2' -dimethyl-4-aminobiphenyl, an aromatic amine colon carcinogen, to investigate the specific role of the acetylator genotype (NAT2) in colon carcinogenesis [17].
• In this paper we report the construction and use of new tester strains of S. typhimurium that express high levels of functional human arylamine N-acetyltransferases, NAT1 and NAT2, retaining characteristic arylamine substrate specificities that are distinct from those of the bacterial enzyme [3].
• The genetic predisposition of rapid acetylators to colorectal cancers suggests localized metabolic activation of arylamine carcinogen metabolites by polymorphic N-acetyltransferase (NAT2) in colon tissues [18].

Anatomical context of aniline

• This radioligand, which possesses an arylamine moiety, may then be covalently incorporated into the receptor binding subunit (58,000 Mr peptide) of the frog erythrocyte membranes by the use of the bifunctional photoactive crosslinker N-succinimidyl-6-(4'-azido-2'- nitrophenylamino)hexanoate (SANAH) [19].
• Expression of arylamine N-acetyltransferases in pre-term placentas and in human pre-implantation embryos [20].
• Four of the bladder cytosols had mean activities significantly (P less than 0.01) higher (approximately 10-fold) than the mean NAT activities of the other five bladder cytosols towards each arylamine carcinogen [16].
• Unscheduled DNA synthesis (UDS)-inducing activity was used as a parameter to estimate the abilities of rat mammary epithelial cells and urothelial cells from various species to activate carcinogenic aromatic amine derivatives [21].
• The arylhydroxamic acid acyltransferase, an enzyme that promotes the introduction of arylamine groups into nucleic acids, is greater in the stomach, small intestine, colon, and lung of the Sprague-Dawley rat than in comparable tissues of Fischer animals [22].

Associations of aniline with other chemical compounds

• l-Isoproterenol was covalently coupled via an azo linkage to soluble copolypeptides of molecular weight 1500 and 10,000 containing an aromatic amine [23].
• N-Acetyltransferase activity (arylamine acetyltransferase; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) and melatonin content are 15-fold higher at night than during the day in a cycle of a 4-fold increase during the subjective night [24].
• The ability of organ cultures of normal human and rat bladder to metabolize the polycyclic hydrocarbon, benzo(a)pyrene (BP), and the arylamine, 2-acetylaminofluorene, has been studied [25].
• These results are consistent with involvement of bladder transitional epithelial prostaglandin H synthase in the genesis of primary aromatic amine-induced bladder cancer [26].
• Human bladder cytosol from nine fresh autopsy specimens were investigated for NAT activity towards p-aminobenzoic acid, and the arylamine carcinogens 4-aminobiphenyl, 2-aminofluorene, and beta-naphthylamine [16].

Gene context of aniline

• The single coding exons of the cloned genes encoding two human arylamine N-acetyltransferases (NAT1 and NAT2) were amplified by expression-cassette polymerase chain reaction and subcloned into the tac promoter-based phagemid vector pKEN2 for production of the recombinant proteins in Escherichia coli strain XA90 [27].
• Human N-acetyltransferase type 1 (NAT1) catalyses the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens [28].
• Combined analyses of different alleles of carcinogenic aromatic amine-activating phase II enzymes were applied to urothelial cancer risk for the first time and showed the highest risk combination of ST1A3 and NAT2 alleles [29].
• Renal interstitial fibrosis based on the interstitial area stained with Aniline-blue or Sirius red solution was significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice [30].
• N-acetyltransferase activity toward the aromatic amine carcinogen 4-aminobiphenyl and O-acetyltransferase activity toward its proximate metabolite N-hydroxy-4-aminobiphenyl were both present in tissue cytosols of WT mice but were undetectable in Nat2 KO mice [31].

Analytical, diagnostic and therapeutic context of aniline

• At this dose and collection period, the lower limit of normal (mean - 2 SD) for the control group was 57%; none of the healthy volunteers had 6-h arylamine excretion rates less than 50% [32].
• Epithelial cultures established from adult rat liver and from rat hepatomas induced in vivo with aromatic amine carcinogens have been compared by light and electron microscopy and by growth properties in liquid medium and in agar [33].
• Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase [34].
• Capillary liquid chromatography/microelectrospray-mass spectrometry (capillary LC/muESI-MS) was used to quantify DNA adducts of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of male Fischer-344 rats [35].
• These findings lend mechanistic support for human epidemiological studies suggesting associations between both rapid and slow acetylator phenotype and cancers related to arylamine exposure [36].

References