Urothelial cell intracytoplasmic inclusions after treatment of promyelocytic leukemia with arsenic trioxide

Whitney R. Wedel, David E. Muirhead, Lora L Arnold, Puttappa R. Dodmane, Subodh M Lele, Lori J Maness-Harris, Rose Hoyt, Samuel Monroe Cohen

Research output: Contribution to journalArticle

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Abstract

Intramitochondrial inclusions containing arsenite that occur within urothelial cells have been previously described in mice exposed to high concentrations of arsenic but not in rats. In epidemiology studies, similar urothelial cell inclusions have also been observed in the urine of humans exposed to high concentrations of arsenic in the drinking water; however, these inclusions were mistakenly identified as micronuclei. To further examine the urothelial cell inclusions that occur in inorganic arsenic-exposed humans, we evaluated two patients with a history of acute promyelocytic leukemia treated for disease relapse with a combination of all-trans retinoic acid and arsenic trioxide. Posttreatment examination of the patients' urine cytology specimens by light and electron microscopy demonstrated cytoplasmic inclusions in exfoliated superficial urothelial cells similar to those seen in mice. The inclusions were present in decreasing quantities at 3 and 7 months after completion of treatment. No comparable inclusions were detected in exfoliated urothelial cells in urine from six individuals not treated with arsenic trioxide. Based on the results of the examination by light and electron microscopy, we have determined that urothelial cell inclusions in the urine of humans previously identified as micronuclei are instead intracytoplasmic inclusions similar to those found in arsenic-treated mice.

Original languageEnglish (US)
Pages (from-to)271-275
Number of pages5
JournalToxicological Sciences
Volume134
Issue number2
DOIs
StatePublished - Aug 1 2013

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Leukemia
Arsenic
Urine
Electron Microscopy
Therapeutics
Light
Acute Promyelocytic Leukemia
Electron microscopy
Optical microscopy
Inclusion Bodies
Tretinoin
Cytology
Drinking Water
Cell Biology
arsenic trioxide
Epidemiology
Recurrence
Rats

Keywords

  • Arsenic trioxide
  • Bladder
  • Urothelial cell

ASJC Scopus subject areas

  • Toxicology

Cite this

Urothelial cell intracytoplasmic inclusions after treatment of promyelocytic leukemia with arsenic trioxide. / Wedel, Whitney R.; Muirhead, David E.; Arnold, Lora L; Dodmane, Puttappa R.; Lele, Subodh M; Maness-Harris, Lori J; Hoyt, Rose; Cohen, Samuel Monroe.

In: Toxicological Sciences, Vol. 134, No. 2, 01.08.2013, p. 271-275.

Research output: Contribution to journalArticle

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