Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice

Takamasa Ohnishi, Lora L Arnold, Jun He, Nicole M. Clark, Shin Kawasaki, Stephen I. Rennard, Craig W. Boyer, Samuel Monroe Cohen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalToxicology
Volume241
Issue number1-2
DOIs
StatePublished - Nov 20 2007

Fingerprint

Tobacco
Inbred C57BL Mouse
Smoke
Inhalation
Endothelium
Urinary Bladder
Epithelium
Tobacco Products
Labeling
Cytotoxicity
Urothelium
Hyperplasia
Inhalation Exposure
Endothelial cells
Cell proliferation
Bromodeoxyuridine
Urinary Bladder Neoplasms
Carcinogens
Electron Scanning Microscopy
Optical microscopy

Keywords

  • Bladder
  • Cell proliferation
  • Tobacco smoke

ASJC Scopus subject areas

  • Toxicology

Cite this

Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice. / Ohnishi, Takamasa; Arnold, Lora L; He, Jun; Clark, Nicole M.; Kawasaki, Shin; Rennard, Stephen I.; Boyer, Craig W.; Cohen, Samuel Monroe.

In: Toxicology, Vol. 241, No. 1-2, 20.11.2007, p. 58-65.

Research output: Contribution to journalArticle

Ohnishi, Takamasa ; Arnold, Lora L ; He, Jun ; Clark, Nicole M. ; Kawasaki, Shin ; Rennard, Stephen I. ; Boyer, Craig W. ; Cohen, Samuel Monroe. / Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice. In: Toxicology. 2007 ; Vol. 241, No. 1-2. pp. 58-65.
@article{37a4a14ab799464ca4d497f09807aa66,
title = "Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice",
abstract = "Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration.",
keywords = "Bladder, Cell proliferation, Tobacco smoke",
author = "Takamasa Ohnishi and Arnold, {Lora L} and Jun He and Clark, {Nicole M.} and Shin Kawasaki and Rennard, {Stephen I.} and Boyer, {Craig W.} and Cohen, {Samuel Monroe}",
year = "2007",
month = "11",
day = "20",
doi = "10.1016/j.tox.2007.08.088",
language = "English (US)",
volume = "241",
pages = "58--65",
journal = "Toxicology",
issn = "0300-483X",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice

AU - Ohnishi, Takamasa

AU - Arnold, Lora L

AU - He, Jun

AU - Clark, Nicole M.

AU - Kawasaki, Shin

AU - Rennard, Stephen I.

AU - Boyer, Craig W.

AU - Cohen, Samuel Monroe

PY - 2007/11/20

Y1 - 2007/11/20

N2 - Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration.

AB - Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration.

KW - Bladder

KW - Cell proliferation

KW - Tobacco smoke

UR - http://www.scopus.com/inward/record.url?scp=35349029327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35349029327&partnerID=8YFLogxK

U2 - 10.1016/j.tox.2007.08.088

DO - 10.1016/j.tox.2007.08.088

M3 - Article

C2 - 17897767

AN - SCOPUS:35349029327

VL - 241

SP - 58

EP - 65

JO - Toxicology

JF - Toxicology

SN - 0300-483X

IS - 1-2

ER -