Speciation Analysis and Environment

Effects of exogenous cysteine on inorganic and organic arsenicals-induced cytolethality†

  1. Teruaki Sakurai1,*,
  2. Chikara Kojima1,
  3. Michael P. Waalkes2,
  4. Seiichiro Himeno1

Article first published online: 15 MAY 2006

DOI: 10.1002/aoc.1072

Issue

Applied Organometallic Chemistry

Applied Organometallic Chemistry

Special Issue: Special issue including information from the 12th Symposium of the Japanese Arsenic Scientists' Society (JASS) held 5–6 November 2005 in Takizawa, Iwate Prefecture, Japan

Volume 20, Issue 9, pages 549–556, September 2006

Additional Information

How to Cite

Sakurai, T., Kojima, C., Waalkes, M. P. and Himeno, S. (2006), Effects of exogenous cysteine on inorganic and organic arsenicals-induced cytolethality. Appl. Organometal. Chem., 20: 549–556. doi: 10.1002/aoc.1072

Author Information

  1. 1

    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan

  2. 2

    Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA

*Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.

  1. †

    This paper is based on work presented at the 12th Symposium of the Japanese Arsenic Scientists' Society (JASS) held 5-6 November 2005 in Takizawa, Iwate Prefecture, Japan

Publication History

  1. Issue published online: 17 AUG 2006
  2. Article first published online: 15 MAY 2006
  3. Manuscript Accepted: 2 MAR 2006
  4. Manuscript Received: 20 DEC 2005

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Keywords:

  • arsenic;
  • cysteine;
  • dimethylarsinic;
  • monomethylarsonic;
  • Cys;
  • Cys conjugate

Abstract

Inorganic arsenicals are distinctly toxic and carcinogenic to humans. Inorganic arsenite (AsIII) and arsenate (AsV) are enzymatically methylated to monomethylarsonic acid (MMAsV) and dimethylarsinic acid (DMAsV) in mammals. Recent reports indicate that cytotoxic trivalent methylated arsenicals are produced through methylation of inorganic arsenicals and are involved in arsenic poisoning. Some previous studies have suggested that a typical thiol reagent cysteine (Cys) can reduce pentavalent arsenicals to trivalent arsenicals and might be able to enhance arsenic cytolethality. However, not much is known concerning the effects of exogenous Cys on the cytolethality of arsenicals. In this study, we examined the effects of exogenous Cys on the cytolethality induced by inorganic and organic arsenicals using rat liver cells. Cys prevented inorganic AsIII-induced cytolethality. In contrast, when more than 5 mM Cys was incubated with millimolar levels of MMAsV or DMAsV, MMAsV- and DMAsV-induced cytolethality significantly increased; this cytolethality might have been caused by the generation of trivalent methylated arsenicals. However, Cys at a concentration of less than 5 mM decreased the MMAsV- and DMAsV-induced cytolethality. These findings suggest that high concentrations of both arsenicals and Cys are required to form trivalent methylated arsenicals and to induce significant cytolethality. Copyright © 2005 John Wiley & Sons, Ltd.

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