Activation of 3‐nitrobenzanthrone and its metabolites by human acetyltransferases, sulfotransferases and cytochrome P450 expressed in Chinese hamster V79 cells

@article{Arlt2003ActivationO3,
  title={Activation of 3‐nitrobenzanthrone and its metabolites by human acetyltransferases, sulfotransferases and cytochrome P450 expressed in Chinese hamster V79 cells},
  author={Volker Manfred Arlt and Hansruedi Glatt and Eva Muckel and Ulrike Pabel and Bernd L. Sorg and Albrecht Seidel and Heinz Frank and Heinz H. Schmeiser and David H. Phillips},
  journal={International Journal of Cancer},
  year={2003},
  volume={105}
}
3‐Nitrobenzanthrone (3‐NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and ambient air pollution. 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. Recently we found that 3‐NBA and its metabolites (3‐ABA, 3‐Ac‐ABA and N‐Ac‐N‐OH‐ABA) form the same DNA adducts in vivo in rats. In order to investigate whether human cytochrome P450 (CYP) enzymes… 
Identification of three major DNA adducts formed by the carcinogenic air pollutant 3‐nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenine
3‐Nitrobenzanthrone (3‐NBA) is a potent mutagen and potential human carcinogen identified in diesel exhaust and ambient air particulate matter. Previously, we detected the formation of 3‐NBA‐derived
Cytosols Acetyltransferases and Sulfotransferases in Human Hepatic NAD ( P ) H : Quinone Oxidoreductase and Conjugation by by 3-Nitrobenzanthrone Forms DNA Adducts after Reduction Environmental Pollutant and Potent Mutagen
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.
Tissue‐specific metabolic activation and mutagenicity of 3‐nitrobenzanthrone in Muta™Mouse
TLDR
The relatively high 3‐NBA nitroreductase activity in Muta™Mouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3‐ NBA is readily reduced and activated in vivo.
Molecular mechanism of genotoxicity of the environmental pollutant 3-nitrobenzanthrone.
  • M. Stiborová, V. Arlt, D. Phillips
  • Biology, Chemistry
    Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
  • 2005
TLDR
The results suggest that both CYPs and peroxidases may play an important role in metabolism of 3-ABA to reactive species forming DNA adducts, participating in genotoxicity of this compound and its parental counterpart, 3-NBA.
Role of Human Aldo-Keto Reductases in the Metabolic Activation of the Carcinogenic Air Pollutant 3-Nitrobenzanthrone.
TLDR
The data suggest that the combined activities of AKR1C1-1C3 and NQO1 contribute equally to the reduction of 3-NBA in A549 and HBEC3-KT cell lines and together represent approximately 50% of the intracellular nitroreductase activity toward 3- NBA.
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.
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