Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice

Masanao Yokohira, Lora L Arnold, Karen L. Pennington, Shugo Suzuki, Satoko Kakiuchi-Kiyota, Karen Herbin-Davis, David J. Thomas, Samuel Monroe Cohen

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, female As3mt knockout (KO) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite administration on the urothelium are dose dependent. Female wild-type C57BL/6 mice and As3mt KO mice were divided into five groups (n = 7) with free access to drinking water containing 0, 1, 10, 25, or 50 ppm arsenic as arsenite for 4 weeks. At sacrifice, urinary bladders of both As3mt KO and wild-type mice showed hyperplasia by light microscopy; however, the hyperplasia was more severe in the As3mt KO mice. Intracytoplasmic granules were detected in the urothelium of As3mt KO and wild-type mice at arsenic doses ≥ 10 ppm but were more numerous, more extensive, and larger in the KO mice. A no effect level for urothelial effects was identified at 1 ppm arsenic in the wild-type and As3mt KO mice. In As3mt KO mice, livers showed mild acute inflammation and kidneys showed hydronephrosis. The present study shows a dose-response for the effects of orally administered arsenite on the bladder urothelium of wildtype and As3mt KO mice, with greater effects in the KO strain but with a no effect level of 1 ppm for both.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalToxicological Sciences
Volume121
Issue number2
DOIs
StatePublished - Jun 6 2011

Fingerprint

Methyltransferases
Arsenic
Knockout Mice
Drinking Water
Urinary Bladder
Epithelium
Oxidation
Urothelium
Hyperplasia
Nutrition
Metabolites
Liver
Optical microscopy
Toxicity
sodium arsenite
Hydronephrosis
Inbred C57BL Mouse
arsenite
Microscopy
Enzymes

Keywords

  • Arsenic methyltransferase
  • Arsenite
  • Bladder
  • Hyperplasia
  • Mouse
  • Toxicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice. / Yokohira, Masanao; Arnold, Lora L; Pennington, Karen L.; Suzuki, Shugo; Kakiuchi-Kiyota, Satoko; Herbin-Davis, Karen; Thomas, David J.; Cohen, Samuel Monroe.

In: Toxicological Sciences, Vol. 121, No. 2, 06.06.2011, p. 257-266.

Research output: Contribution to journalArticle

Yokohira, Masanao ; Arnold, Lora L ; Pennington, Karen L. ; Suzuki, Shugo ; Kakiuchi-Kiyota, Satoko ; Herbin-Davis, Karen ; Thomas, David J. ; Cohen, Samuel Monroe. / Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice. In: Toxicological Sciences. 2011 ; Vol. 121, No. 2. pp. 257-266.
@article{6b5558e9bab146fb949afeb5c05cc6de,
title = "Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice",
abstract = "The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, female As3mt knockout (KO) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite administration on the urothelium are dose dependent. Female wild-type C57BL/6 mice and As3mt KO mice were divided into five groups (n = 7) with free access to drinking water containing 0, 1, 10, 25, or 50 ppm arsenic as arsenite for 4 weeks. At sacrifice, urinary bladders of both As3mt KO and wild-type mice showed hyperplasia by light microscopy; however, the hyperplasia was more severe in the As3mt KO mice. Intracytoplasmic granules were detected in the urothelium of As3mt KO and wild-type mice at arsenic doses ≥ 10 ppm but were more numerous, more extensive, and larger in the KO mice. A no effect level for urothelial effects was identified at 1 ppm arsenic in the wild-type and As3mt KO mice. In As3mt KO mice, livers showed mild acute inflammation and kidneys showed hydronephrosis. The present study shows a dose-response for the effects of orally administered arsenite on the bladder urothelium of wildtype and As3mt KO mice, with greater effects in the KO strain but with a no effect level of 1 ppm for both.",
keywords = "Arsenic methyltransferase, Arsenite, Bladder, Hyperplasia, Mouse, Toxicity",
author = "Masanao Yokohira and Arnold, {Lora L} and Pennington, {Karen L.} and Shugo Suzuki and Satoko Kakiuchi-Kiyota and Karen Herbin-Davis and Thomas, {David J.} and Cohen, {Samuel Monroe}",
year = "2011",
month = "6",
day = "6",
doi = "10.1093/toxsci/kfr051",
language = "English (US)",
volume = "121",
pages = "257--266",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice

AU - Yokohira, Masanao

AU - Arnold, Lora L

AU - Pennington, Karen L.

AU - Suzuki, Shugo

AU - Kakiuchi-Kiyota, Satoko

AU - Herbin-Davis, Karen

AU - Thomas, David J.

AU - Cohen, Samuel Monroe

PY - 2011/6/6

Y1 - 2011/6/6

N2 - The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, female As3mt knockout (KO) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite administration on the urothelium are dose dependent. Female wild-type C57BL/6 mice and As3mt KO mice were divided into five groups (n = 7) with free access to drinking water containing 0, 1, 10, 25, or 50 ppm arsenic as arsenite for 4 weeks. At sacrifice, urinary bladders of both As3mt KO and wild-type mice showed hyperplasia by light microscopy; however, the hyperplasia was more severe in the As3mt KO mice. Intracytoplasmic granules were detected in the urothelium of As3mt KO and wild-type mice at arsenic doses ≥ 10 ppm but were more numerous, more extensive, and larger in the KO mice. A no effect level for urothelial effects was identified at 1 ppm arsenic in the wild-type and As3mt KO mice. In As3mt KO mice, livers showed mild acute inflammation and kidneys showed hydronephrosis. The present study shows a dose-response for the effects of orally administered arsenite on the bladder urothelium of wildtype and As3mt KO mice, with greater effects in the KO strain but with a no effect level of 1 ppm for both.

AB - The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, female As3mt knockout (KO) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite administration on the urothelium are dose dependent. Female wild-type C57BL/6 mice and As3mt KO mice were divided into five groups (n = 7) with free access to drinking water containing 0, 1, 10, 25, or 50 ppm arsenic as arsenite for 4 weeks. At sacrifice, urinary bladders of both As3mt KO and wild-type mice showed hyperplasia by light microscopy; however, the hyperplasia was more severe in the As3mt KO mice. Intracytoplasmic granules were detected in the urothelium of As3mt KO and wild-type mice at arsenic doses ≥ 10 ppm but were more numerous, more extensive, and larger in the KO mice. A no effect level for urothelial effects was identified at 1 ppm arsenic in the wild-type and As3mt KO mice. In As3mt KO mice, livers showed mild acute inflammation and kidneys showed hydronephrosis. The present study shows a dose-response for the effects of orally administered arsenite on the bladder urothelium of wildtype and As3mt KO mice, with greater effects in the KO strain but with a no effect level of 1 ppm for both.

KW - Arsenic methyltransferase

KW - Arsenite

KW - Bladder

KW - Hyperplasia

KW - Mouse

KW - Toxicity

UR - http://www.scopus.com/inward/record.url?scp=79957793793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957793793&partnerID=8YFLogxK

U2 - 10.1093/toxsci/kfr051

DO - 10.1093/toxsci/kfr051

M3 - Article

VL - 121

SP - 257

EP - 266

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -