Benzene Induces Cytotoxicity without Metabolic Activation

• Nishikawa Takuro

  Departments of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University

• Izumo Kimiko

  Departments of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University

• Miyahara Emiko

  Departments of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University

• Horiuchi Masahisa

  Departments of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University

• Okamoto Yasuhiro

  Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University

• Kawano Yoshifumi

  Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University

• Takeuchi Toru

  Departments of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University

Abstract

Objectives: Benzene has been consistently associated with hematological disorders, including acute myeloid leukemia and aplastic anemia, but the mechanisms causing these disorders are still unclear. Various metabolites of benzene lead to toxicity through the production of reactive oxygen species (ROS), the inhibition of topoisomerase and DNA damage. However, benzene itself is considered to have no mutagenic or cytotoxic activity. In this study, we investigated the effects of benzene itself on a human myeloid cell line with or without benzene metabolizing enzyme inhibitors. Methods: A human myeloid cell line, HL-60, was exposed to benzene with or without cytochrome P450 2E1 or myeloperoxidase inhibitor. Cytotoxicity was evaluated in terms of global DNA methylation levels, induction of apoptosis, and ROS production. Results: Benzene did not change global DNA methylation levels. However, benzene itself increased the levels of apoptosis and ROS. This cytotoxicity did not change with the addition of benzene metabolizing enzyme inhibitors. Benzene itself increased the mRNA levels of oxidative stress-related genes and transcription factors of activator protein-1. Conclusions: Benzene did not influence global DNA methylation in HL-60 cells, but had cytotoxic effects and changed gene expression levels. To elucidate the mechanisms of benzene toxicity, benzene itself as well as benzene metabolites must be investigated.<br>

Journal

• Journal of Occupational Health

  Journal of Occupational Health 53 (2), 84-92, 2011

  Japan Society for Occupational Health

Keywords

• Apoptosis
• Benzene
• Cytotoxicity
• DNA methylation
• HL-60 cells
• Reactive oxygen species

Details

• CRID: 1390001204454896000
• NII Article ID: 10027959345
• NII Article ID: 130004447538
• NII Book ID: AA11090645
• DOI: 10.1539/joh.10-002-oa
• ISSN: 13489585
• ISSN: 13419145
• NDL BIB ID: 11127798
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11127798
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1539%2Fjoh.10-002-OA
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1539/joh.10-002-OA
• Web Site: https://search.jamas.or.jp/link/ui/2011336622
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed