ToxSci Advance Access published online on July 25, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg198
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cell Biology and Anatomy, Southwest Environmental Health Science Center, PO Box 245044, The University of Arizona, Tucson, AZ 85724
* To whom correspondence should be addressed. E-mail: lantz{at}email.arizona.edu.
Vinyl acetate is a synthetic organic ester that has been shown to produce nasal tumors in rats following exposure to 600 ppm in air. The proposed mechanism of action involves metabolism of vinyl acetate by carboxylesterases and the production of protons leading to cellular acidification. While vinyl acetate-induced decreases in intracellular pH (pHi) have been demonstrated in rat hepatocytes, comparable data from nasal epithelial cells do not exist. Using an in vitro assay system, we have determined the effects of vinyl acetate exposure on pHi in respiratory and olfactory nasal epithelial cells from rat. Respiratory and olfactory epithelial cells were isolated from dissected maxillo- and ethmoturbinates by enzyme digestion. Cells were plated, loaded with the pH sensitive dye, carboxyseminaphthorhodafluor-1 (SNARF-1), and observed using confocal microscopy. Individual cellular analysis demonstrated that both respiratory and olfactory epithelial cells responded to vinyl acetate exposures with a dose-dependent decrease in pHi. Changes occurred at 100 µM but reached a plateau above 250 µM. Maximal decreases in pHi were 0.3 pH units in respiratory epithelial cells. While pHi values were normally distributed for respiratory epithelial cells, olfactory epithelial cells demonstrated a bimodal distribution, indicating at least two populations of cells, with only one population of cells responding to vinyl acetate. Acidification in these cells did not plateau, but continued to increase at 1000 µM. Bis(p-nitrophenyl)phosphate (BNPP), a carboxylesterase inhibitor, was able to attenuate the vinyl acetate-induced decrease in pHi. Data obtained from isolated cells were validated using tissue explants. These results are consistent with the proposed mode of action for vinyl acetate and supply further data for developing appropriate risk assessments for vinyl acetate exposure.
© 2003 Society of Toxicology
Respiratory Toxicology
Vinyl Acetate Decreases Intracellular pH in Rat Nasal Epithelial Cells
2 DuPont Haskell Laboratory for Health and Environmental Sciences, E. I. DuPont de Nemours and Co., Inc., PO Box 50, Newark, DE 19714
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. D. Schroeter, J. S. Kimbell, A. M. Bonner, K. C. Roberts, M. E. Andersen, and D. C. Dorman Incorporation of Tissue Reaction Kinetics in a Computational Fluid Dynamics Model for Nasal Extraction of Inhaled Hydrogen Sulfide in Rats Toxicol. Sci., March 1, 2006; 90(1): 198 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Andersen, R. W. Lutz, K. H. Liao, and W. K. Lutz Dose-Incidence Modeling: Consequences of Linking Quantal Measures of Response to Depletion of Critical Tissue Targets Toxicol. Sci., January 1, 2006; 89(1): 331 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Hinderliter, K. D. Thrall, R. A. Corley, L. J. Bloemen, and M. S. Bogdanffy Validation of Human Physiologically Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data Toxicol. Sci., May 1, 2005; 85(1): 460 - 467. [Abstract] [Full Text] [PDF]
|
|