17117-34-9

A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterize the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 μM (environmentally relevant) to 80 μM by utilizing toxicological and metabolomic approaches. We observed that the RT4 cells were capable of bioactivation of 3-NBA within 30 min of exposure. Activity measurements of various enzymes involved in the conversion of 3-NBA in RT4 cells demonstrated NAD(P)H:quinone oxidoreductase (NQO1) as the main contributor for its bioactivation. Moreover, cytotoxicity assessment exhibited an initiation of adaptive mechanisms at low dosages, which diminished at higher doses, indicating that the capacity of these mechanisms no longer suffices, resulting in increased levels of intracellular reactive oxygen species, reduced proliferation, and hyperpolarisation of the mitochondrial membrane. To characterize the underlying mechanisms of this cellular response, the metabolism of 3-NBA and metabolomic changes in the cells were analyzed. The metabolomic analysis of the cells (0.0003, 0.01, 0.08, 10, and 80 μM 3-NBA) showed elevated levels of various antioxidants at low concentrations of 3-NBA. However, at higher exposure concentrations, it appeared that the cells reprogrammed their metabolism to maintain the cell homeostasis via activation of pentose phosphate pathway (PPP).

The covalent binding of an N-hydroxy metabolite of the powerfully mutagenic 3-nitrobenzanthrone (NBA) to 2'-deoxyguanosine (dG) and calf thymus DNA has been investigated in vitro. The major adduct obtained from the reaction of the N-acetoxy-N-acetyl derivative (N-Aco-N-Ac-ABA) of 3- aminobenzanthrone (ABA) and dG was identified as N-acetyl-3-amino-2-(2'- deoxyguanosin-8-yl)benzanthrone (dG-N-Ac-ABA) by 1H NMR and mass spectroscopies as well as by the reaction of N-Aco-N-Ac-ABA with the double- stranded calf thymus DNA. The coupling with the dG moiety occurred exclusively at C-2 of benzanthrone (BA), suggesting a significant contribution of a resonance-stabilized arenium ion intermediate derived from BA to the production of this new type of adduct. The preferred conformation of the adduct has been shown to be syn by 1H and 13C NMR.

Polycyclic aromatic hydrocarbons (PAH) and nitrated polycyclic aromatic compounds (nitro-PAC) have been found to be mutagenic in bacterial and human cells as well as carcinogenic in rodents. In this investigation, the genotoxic effects of 3-nitrobenzanthrone (3NB) and a mixture of nitropyrene lactones (NPLs) were determined using forward mutation assays performed in two human B-lymphoblastoid cell lines, MCL-5 and h1A1v2, which are responsive to the nitro-PAC class of compounds. Mutagenicity of the compounds was determined at the heterozygous tk locus and the hemizygous hprt locus, thus, identifying both large-scale loss of heterozygosity (LOH) events as well as intragenic mutagenic events. Genotoxicity was also determined using the CREST modified micronucleus assay, which detects chromosomal loss and breakage events. Results indicate 3NB is an effective human cell mutagen, significantly inducing mutations at the tk and hprt loci in both cell lines, and inducing micronuclei in the h1A1v2 cell line. The NPL isomers are also mutagenic, inducing mutations at the two loci as well as micronuclei in both cell lines. Because of their mutagenic potencies and their presence in ambient air, further assessments should be made of human exposures to these nitro-PAC and the potential health risks involved. (C) 2000 Elsevier Science B.V.

Ultrafast time resolved fluorescence anisotropy decay measurements were performed to gain insight into the energy gap dependence of donor-acceptor inter-chromophoric coupling within one supra-molecule. Three new compounds, each consisting of two semi-rigidly linked and strongly coupled chromophores, were designed and synthesized for this study. Their general structure is donor-spacer-acceptor, where "donor" is phenylamino, pyrenylamino, or benzanthronylamino moiety, and acceptor is aminobenzanthrone. While being similar structurally, the compounds differ significantly in the excitation energy difference of the two chromophores in a supra-molecule. Experimental data show an ultrafast initial fluorescence emission anisotropy decrease (within less then 1 ps) when the excited state energies of the interacting chromophores are close to each other or equal. No such fast fluorescence anisotropy dynamics is observed for a compound with a large energy gap.

The reaction of benzanthrone (7H-benz[d,e]anthracen-7-one, 1) with nitrogen dioxide alone or in admixture with ozonized oxygen has been investigated in polar and nonpolar organic solvents at different temperatures. A remarkable change of product distribution was observed depending on the solvent employed; 3-nitrobenzanthrone (4) was the main product from the reaction in dichloromethane, while 2-nitrobenzanthrone was obtained as the major product in tetrachloromethane. Addition of protonic acid or inorganic solid support was found to promote the reaction, favoring the formation of the former nitro compound at the expense of the latter. All major products were identified. The variation of isomer distribution depending on the conditions employed has been discussed in terms of the competition between the homolytic and heterolytic mechanisms involved in the nitration of ketone 1. On the basis of the results obtained, the atmospheric formation of the genotoxic nitro ketone 4 has been briefly discussed.

Five mononitro-, three dinitro- and one trinitrobenzanthrones have been synthesized by the modified Ullmann cross-coupling reaction between nitro-substituted 1-iodonaphthalene and methyl 2-iodobenzoates, followed by the Friedel-Crafts ring closure of the resulting 2-(1-naphthyl)benzoic acid derivatives.

3-Nitrobenzanthrone (3-nitro-7H-benz[d,e]anthracen-7-one) was isolated from the organic extracts of both diesel exhaust and airborne particles and was identified as a new class of powerful direct mutagen. Its mutagenicity by Ames Salmonella assay is very high (208 000 revertants/nmol in Salmonella typhimurium TA98 and 6 290 000 revertants/nmol in YG1024) and compares with that of 1,8-dinitropyrene, which is the direct mutagen of strongest activity (257 000 revertants/nmol in TA98 and 4 780 000 revertants/nmol in YG1024) so far reported in the literature. The new mutagen was also shown to induce micronuclei in mouse peripheral blood reticulocytes after intraperitoneal administration (micronucleated reticulocytes, 0.64% against 25 mg/kg dose after 48 h), suggesting its potential genotoxicity to mammalians. 3- Nitrobenzanthrone is most likely to be formed not only during the combustion process of fossil fuels but also from the atmospheric reaction between benzanthrone and lower oxides of nitrogen, since the latter ketone was found to be nitrated quite easily under an artificial atmosphere containing gaseous NO2 (10 ppm) and O3 (5 ppm) to produce the powerfully mutagenic 3-nitro derivative as the major product, along with several other isomeric mononitrobenzanthrones and dinitro descendants as minor products. 3-Nitrobenzanthrone (3-nitro-7H-benz[d,e]anthracen-7-one) was isolated from the organic extracts of both diesel exhaust and airborne particles end was identified as a new class of powerful direct mutagen. Its mutagenicity by Ames Salmonella assay is very high (208 000 revertants/nmol in Salmonella typhimurium TA98 and 6 290 000 revertants/nmol in YG1024) and compares with that of 1,8-dinitropyrene, which is the direct mutagen of strongest activity (257 000 revertants/nmol in TA98 and 4 780 000 revertants/nmol in YG1024) so far reported in the literature. The new mutagen was also shown to induce micronuclei in mouse peripheral blood reticulocytes after intraperitoneal administration (micronucleated reticulocytes, 0.64% against 25 mg/kg dose after 48 h), suggesting its potential genotoxicity to mammalians. 3-Nitrobenzanthrone is most likely to be formed not only during the combustion process of fossil fuels but also from the atmospheric reaction between benzanthrone and lower oxides of nitrogen, since the letter ketone was found to be nitrated quite easily under an artificial atmosphere containing gaseous NO2 (10 ppm) and O3 (5 ppm) to produce the powerfully mutagenic 3-nitro derivative as the major product, along with several other isomeric mononitrobenzanthrones and dinitro descendants as minor products.

The synthesis of methylimidazo-, phthaloyleneimidazo-, and naphthoyleneimidazobenzanthrones was undertaken.The last two imidazobenzanthrones were obtained by the condensation of phthalic and naphthalic anhydrides with 2,3-diaminobenzanthrone specially prepared for this purpose.The electronic spectra of the obtained compounds were studied.