Disease relevance of beta-Naphthylamine

• Of the dogs given the same dose of 2-naphthylamine for 26 weeks and then kept for 3 years before being killed, 2 dogs had normal bladders but the other 2 had epithelial carcinomas [1].
• Various sulfonic acid derivatives of 1-naphthylamine and 2-naphthylamine were tested in inbred A/St (male and female) mice by the pulmonary adenoma bioassay to determine if this class of compounds, used as intermediates in the dye-stuff industry, possesses tumorigenic activity [2].
• Diethylnitrosamine and dimethylnitrosamine (ID50 between 1 X 10(-4) and 5 X 10(-4) M) and 1- and 2-naphthylamine (ID50 between 1 X 10(-5) and 5 X 10(-4) M) caused inhibition of DNA synthesis at concentrations which overlapped with concentrations that caused measurable toxicity [3].
• All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months [4].
• With the Neisseria species, interpretation of the cinnamaldehyde-coupled beta-naphthylamine reactions was difficult and resulted in profile numbers not listed in the Profile Register. Positive resazurin-glucose reactions resulted in unlisted numbers for all B. catarrhalis strains [5].

High impact information on beta-Naphthylamine

• When examined in a primary culture of human urothelial cells, N-OH-AF, N-OH-AAF, N-OH-ABP, and N-OH-AABP were active, but N-OH-AN, N-OH-AAN, 2-aminonaphthalene (CAS: 91-59-8), 2-aminofluorene (CAS: 153-78-6;), and 4-aminobiphenyl (CAS: 92-67-1) were not [6].
• The metabolic activation of 4-aminobiphenyl, 2-naphthylamine, and several heterocyclic amines has been shown recently to be catalyzed by rat cytochrome P-450ISF-G and by its human ortholog, cytochrome P-450PA [7].
• UGT1A4 P24T and L48V exhibited reduced glucuronidation activities: beta-naphthylamine 30% and 50%, and dihydrotestosterone 50% and 0%, respectively [8].
• Epidemiological studies have established the carcinogenic risk of occupational exposure to aromatic amines such as benzidine, beta-naphthylamine, and 4-aminobiphenyl [9].
• However, the apparent Vmax determinations indicated that the bladders could be classified into rapid or slow acetylator phenotypes based on their NAT activity towards 4-aminobiphenyl, 2-aminofluorene, and beta-naphthylamine [10].

Chemical compound and disease context of beta-Naphthylamine

• Epidemiologic studies have revealed an increased risk for development of transitional cell carcinoma (TCC) among dye workers/painters occupationally exposed to aromatic amines such as benzidine, beta-naphthylamine, orthotoluidine, and aniline [11].
• ST3A1 expressed in Escherichia coli as a fused protein catalyzed sulfation of amines such as PTHP, aniline, 4-chloroaniline, 2-naphthylamine, and desipramine, but barely O-sulfation of typical aryl and hydroxysteroid sulfotransferase substrates [12].
• Oral administration of 2-naphthylamine for 40 weeks plus injections of cyclophosphamide produced bladder carcinomas in 30.8 approximately 35.7% of all animals, associated with downward growth of the bladder epithelium [13].

Biological context of beta-Naphthylamine

• The rates of PAPS-dependent rat liver cytosol-catalyzed esterification of N-hydroxy-N-ethyl-4-aminoazobenzene, N-hydroxy-4-aminoazobenzene, and N-hydroxy-1- and 2-naphthylamine were 20 to 50% of that for N-HO-MAB [14].
• Enzyme purification was facilitated by development of a rapid and sensitive continuous assay using the substrate L-pyroglutamyl-Nim-benzylhistidyl-L-prolyl-beta-naphthylamide, which, upon hydrolysis of the naphthylamide, results in the appearance of the fluorescent product, beta-naphthylamine (beta NA) [15].
• The time course of DNA damage induced by in vivo administration of benzidine, 1- and 2-naphthylamine or dimethylnaphthylamine has been evaluated using an alkaline elution technique [16].
• These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine-exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2-naphthylamine and 4-aminobiphenyl [17].
• Persistent and dose-dependent changes of DNA viscometric parameters, which are considered indicative of DNA fragmentation, were produced by six hepatocarcinogenic aromatic amines: 2-naphthylamine, benzidine, 2,4-diaminotoluene, auramine O, 4-aminoazobenzene, and 4-dimethylaminoazobenzene [18].

Anatomical context of beta-Naphthylamine

• Prostaglandin H synthase and mixed-function oxidase-catalyzed bindings of 2-naphthylamine to protein and to transfer RNA were compared using liver and bladder microsomes [19].
• Metabolism of 1- and 2-naphthylamine in isolated rat hepatocytes [20].
• To test the hypothesis that extracellular generation of an ultimate carcinogenic species can initiate a neoplastic event normal human fibroblasts were exposed to N-hydroxy-1- and 2-naphthylamine (N-HO-1-NA and N-HO-2-NA) at pH 5 and pH 7 [21].
• Our results indicate that, not only enteropeptidase, but also the concerted action of the aminopeptidases of the rat small intestine, can rapidly release 2-naphthylamine from the substrate [22].
• DNA adducts formed by ring-oxidation of the carcinogen 2-naphthylamine with prostaglandin H synthase in vitro and in the dog urothelium in vivo [23].

Associations of beta-Naphthylamine with other chemical compounds

• In the current study, the relationship between acetylator phenotype and susceptibility to the genotoxicities of benzidine, 4-aminobiphenyl, 4,4'-methylenebis-2-chloroaniline, and 2-naphthylamine was investigated [24].
• Four days after single i.p. administrations of 2-aminonaphthalene to C3H mice, the liver content of reduced glutathione and the liver microsomal cytochrome P-450 O-demethylation activity were decreased [25].
• The liver probably plays a major role in the metabolic activation of the bladder carcinogen 2-naphthylamine (2-NA) and in the inactivation of the non-carcinogenic isomer 1-naphthylamine (1-NA) [20].
• A transformable and a non-transformable cell culture were further tested with other carcinogens (3-methylcholanthrene [MCA], benzyl chloride, ethyl-p-toluenesulfonate, 2-naphthylamine, and aflatoxin B1) [26].
• The resulting [L-Asp]3-L-Lys 2-naphthylamide fragment is then degraded by a combination of aminopeptidase A and N to yield free 2-naphthylamine [22].

Gene context of beta-Naphthylamine

• For carbocyclic arylamines such as 4-aminobiphenyl and beta-naphthylamine, the apparent affinity was significantly (P < 0.05) higher for NAT2 than NAT1 [27].
• Human liver arylamine N-sulfotransferase activity. Thermostable phenol sulfotransferase catalyzes the N-sulfation of 2-naphthylamine [28].
• Cell membrane preparations were assayed for NEP activity by incubation with glutaryl-Ala-Ala-Phe-4-methoxy-beta naphthylamide to generate a fluorescent degradation product methoxy 2 naphthylamine [29].
• The inhibitory effect of 2-naphthylamine on both MAO A and B catalytic activity, supports the hypothesis that smoking decreases MAO activity in vivo, instead that smokers with lower MAO activity are more prone to become a smoker [30].
• Although N-acetyltransferase activity was expressed for each of the arylamines tested (i. e., p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, beta-naphthylamine), no correlation was observed between acetylator genotype and expression of human colon arylamine N-acetyltransferase activity [31].

Analytical, diagnostic and therapeutic context of beta-Naphthylamine

• A marker for biological response to bladder carcinogen exposure was evaluated in a cross-sectional study of 504 workers at high risk due to a range of exposures to various carcinogenic aromatic amines, primarily 2-naphthylamine [32].
• The metabolism of benzidine and 2-naphthylamine, two aromatic amines which are carcinogenic for the human, was investigated in human and rat bladder organ cultures [33].
• Determination of 2-naphthylamine in urine by a novel reversed-phase high-performance liquid chromatography method [34].
• Analysis of the derivatized extracts by gas chromatography/negative ion chemical ionization/mass spectrometry demonstrated the presence of aniline, ortho-, meta-, and para-toluidine, 2-naphthylamine, and 4-aminobiphenyl [35].

References