17117-34-9Relevant articles and documents
Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells
Pink, Mario,Verma, Nisha,Zerries, Anna,Schmitz-Spanke, Simone
, p. 1855 - 1864 (2017)
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 genotoxicity of 3-nitrobenzanthrone and the nitropyrene lactones in human lymphoblasts
Phousongphouang, Patricia T,Grosovsky, Andrew J,Eastmond, David A,Covarrubias, Maricela,Arey, Janet
, p. 93 - 103 (2000)
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.
Reaction of Benzanthrone (7H-Benz[d,e]anthracen-7-one) with Nitrogen Dioxide Alone or in Admixture with Ozone. Implications for the Atmospheric Formation of Genotoxic 3-Nitrobenzanthrone
Enya, Takeji,Suzuki, Hitomi,Hisamatsu, Yoshiharu
, p. 2221 - 2228 (2007/10/03)
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.
