Activation of 3-nitrobenzanthrone and its metabolites to DNA-damaging species in human B lymphoblastoid MCL-5 cells.

@article{Arlt2004ActivationO3,
  title={Activation of 3-nitrobenzanthrone and its metabolites to DNA-damaging species in human B lymphoblastoid MCL-5 cells.},
  author={Volker Manfred Arlt and Kathleen J. Cole and David H. Phillips},
  journal={Mutagenesis},
  year={2004},
  volume={19 2},
  pages={
          149-56
        }
}
3-Nitrobenzanthrone (3-NBA) is one of the most potent mutagens in the Ames Salmonella typhimurium assay and a suspected human carcinogen recently identified in diesel exhaust and in airborne particulate matter. 3-Aminobenzanthrone (3-ABA), 3-acetylaminobenzanthrone (3-Ac-ABA) and N-acetyl-N-hydroxy-3-aminobenzanthrone (N-Ac-N-OH-ABA) have been identified as 3-NBA metabolites. In the present study we investigated the genotoxic effects of 3-NBA and its metabolites in the human B lymphoblastoid… 
THE ENVIRONMENTAL POLLUTANT AND CARCINOGEN 3-NITROBENZANTHRONE AND ITS HUMAN METABOLITE 3-AMINOBENZANTHRONE ARE POTENT INDUCERS OF RAT HEPATIC CYTOCHROMES P450 1A1 AND -1A2 AND NAD(P)H:QUINONE OXIDOREDUCTASE
TLDR
It is demonstrated for the first time, to the authors' knowledge, that by inducing hepatic NQO1 and CYP1A1/2, both 3-NBA and 3-ABA increase the enzymatic activation of these two compounds to reactive DNA adduct-forming species, thereby enhancing their own genotoxic potential.
Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols.
TLDR
The role of human hepatic NQO1 is shown to reduce 3- NBA to species being further activated by NATs and SULTs, indicating that 3-NBA is predominantly activated by cytosolic nitroreductases rather than microsomal POR.
Genotoxicity of 3-nitrobenzanthrone and 3-aminobenzanthrone in MutaMouse and lung epithelial cells derived from MutaMouse.
TLDR
The data indicate that MutaMouse FE1 cells are well suited for cost-effective testing of suspected mutagens with different metabolic activation pathways as a guide for subsequent in vivo Muta mouse testing.
The impact of p53 function on the metabolic activation of the carcinogenic air pollutant 3-nitrobenzanthrone and its metabolites 3-aminobenzanthrone and N-hydroxy-3-aminobenzanthrone in human cells
TLDR
The results show that p53’s influence on carcinogen activation depends on the agent studied and thereby on the XMEs that mediate the bioactivation of that particular compound.
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TLDR
Results indicate that O-acetylation and O-sulfonation by human NATs and SULTs may contribute significantly to the high mutagenic and genotoxic potential of 3-NBA.
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TLDR
The covalent binding of an N-hydroxy metabolite of the powerfully mutagenic 3-nitrobenzanthrone to 2'-deoxyguanosine (dG) and calf thymus DNA has been investigated in vitro and the preferred conformation of the adduct has been shown to be syn by 1H and 13C NMR.
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TLDR
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