Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells

Journal article


Publication Details

Author(s): Pink M, Verma N, Zerries A, Schmitz-Spanke S
Journal: Chemical Research in Toxicology
Publication year: 2017
Volume: 30
Journal issue: 10
Pages range: 1855-1864
ISSN: 0893-228X


Abstract

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 ?M (environmentally relevant) to 80 ?M 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 ?M 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).


FAU Authors / FAU Editors

Pink, Mario Dr.
Lehrstuhl für Arbeits- und Sozialmedizin
Schmitz-Spanke, Simone Prof. Dr.
Professur für Biomarker in der Arbeitsmedizin
Verma, Nisha Dr.
Professur für Biomarker in der Arbeitsmedizin
Zerries, Anna
Professur für Biomarker in der Arbeitsmedizin


Additional Organisation
Exzellenz-Cluster Engineering of Advanced Materials


Research Fields

Nanosafety
Exzellenz-Cluster Engineering of Advanced Materials


How to cite

APA:
Pink, M., Verma, N., Zerries, A., & Schmitz-Spanke, S. (2017). Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells. Chemical Research in Toxicology, 30(10), 1855-1864. https://dx.doi.org/10.1021/acs.chemrestox.7b00174

MLA:
Pink, Mario, et al. "Dose-Dependent Response to 3-Nitrobenzanthrone Exposure in Human Urothelial Cancer Cells." Chemical Research in Toxicology 30.10 (2017): 1855-1864.

BibTeX: 

Last updated on 2018-05-10 at 02:25