Cytotoxicity of combinations of arsenicals on rat urinary bladder urothelial cells in vitro

Merielen G. Nascimento, Shugo Suzuki, Min Wei, Ashish Tiwari, Lora L. Arnold, Xiufen Lu, X. Chris Le, Samuel M. Cohen

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in the drinking water is carcinogenic to the urinary bladder of humans. The highly reactive trivalent organic arsenicals dimethylarsinous acid (DMAIII) and monomethylarsonous acid (MMAIII) are formed during the metabolism of inorganic arsenic in vivo in addition to the corresponding mono-, di- and trimethylated pentavalent arsenicals. The objective of this study was to determine if combining arsenicals was additive or synergistic toward inducing cytotoxicity in a rat urothelial cell line. The MYP3 cell line, an immortalized but not transformed rat urinary bladder epithelial cell line, was seeded into appropriate culture wells. Treatment with the arsenicals was begun 24 h after seeding and continued for 3 days. Combinations of arsenicals used were DMAIII with arsenite, dimethylarsinic acid (DMAV) or trimethylarsine oxide (TMAO). Combinations of concentrations used were the LC50, one-quarter or one-half the LC50 of one arsenical with one-half or one-quarter the LC50 of the other arsenical. To determine if MYP3 cells metabolize arsenicals, cells were treated with arsenate, arsenite and MMAV as described above and the medium was analyzed by HPLC-ICPMS to determine species and quantity of arsenicals present. When cells were treated with one-quarter or one-half the LC50 concentration of both arsenicals, the cytotoxicity was approximately the same as when cells were treated with half the LC50 concentration or the LC50 concentration, respectively, of either arsenical. Treatment with one-quarter the LC50 concentration of one arsenical plus the LC50 concentration of a second arsenical had similar cytotoxicity as treatment with the LC50 concentration of either of the arsenicals. Quantitation and speciation of arsenicals in the cell culture medium showed that MYP3 cells have some reductase activity but the cells do not methylate arsenicals. The effect on the cytotoxicity of arsenicals in combination was additive rather than synergistic toward a rat urothelial cell line.

Original languageEnglish (US)
Pages (from-to)69-74
Number of pages6
JournalToxicology
Volume249
Issue number1
DOIs
StatePublished - Jul 10 2008

Keywords

  • Arsenite
  • Dimethylarsinic acid (DMA)
  • Dimethylarsinous acid (DMA)
  • Trimethylarsine oxide (TMAO)
  • Urinary bladder
  • Urothelial cell cytotoxicity

ASJC Scopus subject areas

  • Toxicology

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