Biological Activity of Inorganic Arsenic and Antimony Reflects Oxidation State in Cultured Human Keratinocytes

Timothy J. Patterson, Mai Ngo, Pavel A. Aronov, Tatiana V. Reznikova, Peter G. Green, Robert H. Rice

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Sodium arsenite is much more potent than sodium arsenate in producing adverse effects in animals and in cultured cells. Although arsenate may exhibit toxicity as a phosphate analogue, its potency in vivo appears to be enhanced by reduction to arsenite. To understand the relative importance of this reduction, which is critical in evaluating the responsiveness of cell culture models to the different oxidation states and thus to elucidating the mechanism of arsenic action, present work has correlated the extent of reduction with biological activity in human keratinocytes. The results show that at biologically relevant concentrations, arsenate reduction to appreciable levels required several days, helping rationalize a previous empirical observation that it was approximately one-third as potent as arsenite. The relatively low conversion rate also emphasizes a limitation of culture; arsenate was nearly as efficacious as arsenite, but the time required for it to reach maximal effect exceeded ordinary medium change intervals. In keratinocytes, an important role for purine nucleoside phosphorylase in the reduction could not be demonstrated, indicating that another pathway is dominant in this cell type. Methylation of inorganic arsenic, uptake of methylated forms, and their reduction were all very slow. These findings suggest that the reduced methylated forms have only a small contribution to skin carcinogenesis unless they are supplied through the circulation. In parallel experiments, trivalent antimony was similar to arsenite in potency and efficacy, whereas pentavalent antimony was virtually without biological effect. Conversion of antimony in the pentavalent to the trivalent oxidation state was not detectable in keratinocytes. These findings emphasize the importance of intracellular reduction of the metalloids for biological effects.

Original languageEnglish (US)
Pages (from-to)1624-1631
Number of pages8
JournalChemical Research in Toxicology
Volume16
Issue number12
DOIs
StatePublished - Dec 2003

Fingerprint

Antimony
Arsenic
Bioactivity
Keratinocytes
Oxidation
Metalloids
Purine-Nucleoside Phosphorylase
Human Activities
Methylation
Cultured Cells
Carcinogenesis
Cell Culture Techniques
Phosphates
Observation
Skin
arsenite
Cell culture
Toxicity
Animals
arsenic acid

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Patterson, T. J., Ngo, M., Aronov, P. A., Reznikova, T. V., Green, P. G., & Rice, R. H. (2003). Biological Activity of Inorganic Arsenic and Antimony Reflects Oxidation State in Cultured Human Keratinocytes. Chemical Research in Toxicology, 16(12), 1624-1631. https://doi.org/10.1021/tx034146y

Biological Activity of Inorganic Arsenic and Antimony Reflects Oxidation State in Cultured Human Keratinocytes. / Patterson, Timothy J.; Ngo, Mai; Aronov, Pavel A.; Reznikova, Tatiana V.; Green, Peter G.; Rice, Robert H.

In: Chemical Research in Toxicology, Vol. 16, No. 12, 12.2003, p. 1624-1631.

Research output: Contribution to journalArticle

Patterson, Timothy J. ; Ngo, Mai ; Aronov, Pavel A. ; Reznikova, Tatiana V. ; Green, Peter G. ; Rice, Robert H. / Biological Activity of Inorganic Arsenic and Antimony Reflects Oxidation State in Cultured Human Keratinocytes. In: Chemical Research in Toxicology. 2003 ; Vol. 16, No. 12. pp. 1624-1631.
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