skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

Abstract

A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested thatmore » dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.« less

Authors:
;  [1];  [2];  [1]
  1. Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka (Japan)
  2. Division of Toxicology, Wageningen University, Wageningen (Netherlands)
Publication Date:
OSTI Identifier:
22215961
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BENZOQUINONES; CARCINOMAS; CATTLE; CYSTEINE; ELECTROPHORESIS; GELS; GLUTATHIONE; HUMAN POPULATIONS; NAD; OXIDATION; PHENANTHRENE; PHOSPHORYLATION; SKIN; STRAND BREAKS; TOXICITY

Citation Formats

Toyooka, Tatsushi, Shinmen, Takuya, Aarts, Jac M.M.J.G., and Ibuki, Yuko, E-mail: ibuki@u-shizuoka-ken.ac.jp. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.017.
Toyooka, Tatsushi, Shinmen, Takuya, Aarts, Jac M.M.J.G., & Ibuki, Yuko, E-mail: ibuki@u-shizuoka-ken.ac.jp. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity. United States. doi:10.1016/J.TAAP.2012.08.017.
Toyooka, Tatsushi, Shinmen, Takuya, Aarts, Jac M.M.J.G., and Ibuki, Yuko, E-mail: ibuki@u-shizuoka-ken.ac.jp. Thu . "Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity". United States. doi:10.1016/J.TAAP.2012.08.017.
@article{osti_22215961,
title = {Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity},
author = {Toyooka, Tatsushi and Shinmen, Takuya and Aarts, Jac M.M.J.G. and Ibuki, Yuko, E-mail: ibuki@u-shizuoka-ken.ac.jp},
abstractNote = {A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.},
doi = {10.1016/J.TAAP.2012.08.017},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 264,
place = {United States},
year = {2012},
month = {11}
}