Time Course of Urothelial Changes in Rats and Mice Orally Administered Arsenite

Lora L Arnold, Shugo Suzuki, Masanao Yokohira, Satoko Kakiuchi-Kiyota, Karen L. Pennington, Samuel Monroe Cohen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Inorganic arsenic (arsenite and arsenate) at high exposures is a known human carcinogen, inducing tumors of the urinary bladder, skin, and lungs. In two experiments, we examined the urothelial proliferative effects of treatment with 173 ppm sodium arsenite (100 ppm arsenic) in the drinking water for 6 and 24 hr, and 3, 7, and 14 days in female F344 rats and 43.3 ppm sodium arsenite (25 ppm arsenic) in female C57BL/6 wild-type and arsenic (+3 oxidation state) methyltransferase knockout (As3mt KO) mice that are unable to methylate arsenicals. In the rat and both mouse genotypes, scanning electron microscopy showed cytotoxic urothelial changes as early as 6 hr after the start of arsenic exposure. The severity of AsIII-induced cytotoxic urothelial changes increased over time in the rat and in the As3mt KO mouse. Light microscopy showed an increase in urothelial hyperplasia in the rat. No significant increases in bromodeoxyuridine-labeling index were observed. The data support the hypothesis that the sequence of events in the mode of action for urothelial effects of orally administered inorganic arsenic in the rat and mouse involves superficial cytotoxicity with consequent regenerative increased cell proliferation similar to the findings associated with the administration of dimethylarsinic acid (DMAV) in rats.

Original languageEnglish (US)
Pages (from-to)855-862
Number of pages8
JournalToxicologic Pathology
Volume42
Issue number5
DOIs
StatePublished - Jul 2014

Fingerprint

Arsenic
Rats
Cacodylic Acid
Arsenicals
Inbred F344 Rats
Cell proliferation
Methyltransferases
Bromodeoxyuridine
Cytotoxicity
Drinking Water
Carcinogens
Electron Scanning Microscopy
Labeling
Optical microscopy
Hyperplasia
arsenite
Tumors
Microscopy
Skin
Urinary Bladder

Keywords

  • arsenic
  • cell proliferation
  • cytotoxicity
  • hyperplasia
  • urinary bladder

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

Cite this

Time Course of Urothelial Changes in Rats and Mice Orally Administered Arsenite. / Arnold, Lora L; Suzuki, Shugo; Yokohira, Masanao; Kakiuchi-Kiyota, Satoko; Pennington, Karen L.; Cohen, Samuel Monroe.

In: Toxicologic Pathology, Vol. 42, No. 5, 07.2014, p. 855-862.

Research output: Contribution to journalArticle

Arnold, Lora L ; Suzuki, Shugo ; Yokohira, Masanao ; Kakiuchi-Kiyota, Satoko ; Pennington, Karen L. ; Cohen, Samuel Monroe. / Time Course of Urothelial Changes in Rats and Mice Orally Administered Arsenite. In: Toxicologic Pathology. 2014 ; Vol. 42, No. 5. pp. 855-862.
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