Disease relevance of NSC 11436

• 1-Nitropyrene is slowly reduced by intact cells of Salmonella typhimurium to yield 1-aminopyrene and N-acetyl-1-aminopyrene plus six unidentified minor products [1].
• Photochemical transformation and phototoxicity of 1-aminopyrene [2].
• Ultraviolet radiation increases the toxicity of pyrene, 1-aminopyrene and 1-hydroxypyrene to human keratinocytes [3].

High impact information on NSC 11436

• The present results also demonstrate that, under the conditions of this bioassay, 1-nitropyrene was significantly more carcinogenic than either 1-nitrosopyrene or 1-aminopyrene [4].
• Using an O-acetyltransferase overexpressing Salmonella strain, genotoxic activation of P450 1B1 marker chemicals (1-nitropyrene, 1-aminopyrene and DEPE) by lung, liver and kidney microsomes was increased 1.7-4.2-, 1.4-1.5- and 1.0-1.3-fold, respectively, by exposure to 0.3 mg/m(3) DEP [5].
• The changes in molar enthalpy are relatively comparable in both mobile phases with 1-aminopyrene having values of -5.0 +/- 0.2 kcal/mol in methanol and -6.3 +/- 0.7 kcal/mol in acetonitrile (1 cal = 4.184 J) [6].
• The reduced metabolite of 1-nitropyrene, 1-aminopyrene, was also shown to be activated to a mutagenic metabolite by CYP1A2, using 3T3-1A2 cells in combination with a shuttle vector, and the Amestest in combination with the specific CYP1A2 inhibitor furafylline [7].
• Three different in vitro mutation assays were used to investigate the involvement of cytochrome P450 enzymes in the activation of the nitro-polycyclic aromatic hydrocarbons (nitroPAHs) 1-nitropyrene and 2-nitrofluorene and their reduced metabolites amino-polycyclic aromatic hydrocarbons (aminoPAHs) 1-aminopyrene and 2-aminofluorene [7].

Biological context of NSC 11436

• The results are discussed in terms of the metabolic activation of 1-nitropyrene and 1-aminopyrene in Chinese hamster lung cells [8].
• N-(Pyren-1-yl)-(3R,4S)-4-[(1S,2R)-1,2,3-trihydroxypropyl]pyrrolidin-3-ol (4) was obtained in 36% yield from 3-deoxy-3-C-formyl-1,2:5,6-di-O-isopropylidene-alpha-D-allofuranose (3) by combined hydrolysis and aminoalkylation reactions with 1-aminopyrene in a one-pot reaction [9].

Anatomical context of NSC 11436

• In the feces from conventional rats, substantial nitro reduction and N-acetylation occurred with the major metabolites being: 1-NP greater than 1-aminopyrene greater than 8-acetylaminopyrenol greater than 6-acetylaminopyrenol greater than 3-acetylaminopyrenol [10].
• Hepatocytes of human and rat failed to mediate mutation by 1-aminopyrene (1-AP) [11].
• Minor amounts of 1-aminopyrene and 10-hydroxy-1-nitropyrene were detected in the macrophage incubation medium, and only minute quantities of 1-nitropyrene-4,5-dihydrodiol, 1-aminopyrene, and 10-hydroxy-1-nitropyrene were detected in macrophages [12].
• The data presented here suggest that 1-nitropyrene and 1-aminopyrene are metabolized to reactive intermediates which form different DNA adducts in Chinese hamster lung fibroblasts [13].
• The purpose of this study was to assess the effects of UV-A irradiated pyrene (Pyr), 1-aminopyrene (1-AP) and 1-hydroxypyrene (1-HP) on human keratinocytes, the skin primary site of UV irradiated PAH exposure [3].

Associations of NSC 11436 with other chemical compounds

• Competition studies demonstrate that polycyclic aromatic hydrocarbons (PAHs) (BP > 1-aminopyrene > pyrene > 7,12-dimethylbenz[a]anthracene > 3-methylcholanthrene > benzo[e]pyrene > benzo[g, h, i,]perylene) are the best ligands of the 8 S protein [14].
• Benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, 2-acetylaminofluorene, 2-aminoanthracene, and 1-aminopyrene, when fed to adult Drosophila melanogaster males, gave a negative mutagenic response in the X-linked recessive lethal assay [15].
• For CYP1A2, of the 5 compounds tested [2-aminoanthracene (2AA), 1-aminopyrene, 6-aminochrysene, 2-amino-3-methylimidazo(4,5-f)quinoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)], only the mutagenicity of 2AA was slightly increased ( approximately 1.5-fold) in the presence of b(5) [16].
• Latex was able to bind up to 2.82 x 10(-7) mol of 1-aminopyrene per 1 m2 of the surface of the latex particles due to the ionic interactions between carboxylate anions and ammonium cations of protonated 1-aminopyrene [17].
• Depending on pH, 1-aminopyrene interacts with both surface attached CD and DNA by electrostatic bonds and supramolecular complexation while 1-hydroxypyrene associates with the CD hosts via complexation [18].

Gene context of NSC 11436

• It was shown that the CBP bound the environmental carcinogen 1-nitropyrene, its reduced metabolite 1-aminopyrene and the ultimate carcinogenic metabolite of benzo[a]pyrene or (+)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene but not the smaller coplanar PCB molecule, 3,3',4,4'-tetrachlorobiphenyl [19].

Analytical, diagnostic and therapeutic context of NSC 11436

• High-pressure liquid chromatography analysis showed that 1-NP was converted by S9 mix to several metabolites, including 1-aminopyrene (AP) [20].
• The former metabolite was identified as 1-aminopyrene and the latter two metabolites as 1-acetylaminopyrene and 1-formylaminopyrene by comparing their mass and UV spectra, and their behaviors in HPLC and TLC, with those of authentic samples [21].
• This study presents a sensitive and selective method for detection of Hb adducts after oral administration of a single dose 1-NP to rats, by measuring 1-aminopyrene (1-AP) after in vitro hydrolysis of the adducts [22].

References