Inorganic arsenic as a developmental toxicant: In utero exposure and alterations in the developing rat lungs

Jay S. Petrick, Francoise M. Blachere, Ornella Selmin, Robert Clark Lantz

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the b-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers.

Original languageEnglish (US)
Pages (from-to)583-591
Number of pages9
JournalMolecular Nutrition and Food Research
Volume53
Issue number5
DOIs
StatePublished - May 2009

Fingerprint

Arsenic
arsenic
toxic substances
lungs
Lung
rats
Drinking Water
drinking water
protein synthesis
Catenins
arsenites
Proteins
Poisons
integrins
lung neoplasms
Gene Library
cell movement
Integrins
cDNA libraries
respiratory tract diseases

Keywords

  • Arsenic
  • Lung development
  • Microarray
  • Protein array

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

Inorganic arsenic as a developmental toxicant : In utero exposure and alterations in the developing rat lungs. / Petrick, Jay S.; Blachere, Francoise M.; Selmin, Ornella; Lantz, Robert Clark.

In: Molecular Nutrition and Food Research, Vol. 53, No. 5, 05.2009, p. 583-591.

Research output: Contribution to journalArticle

@article{6d77a622a41a4cb8a8f4f39eab93717c,
title = "Inorganic arsenic as a developmental toxicant: In utero exposure and alterations in the developing rat lungs",
abstract = "In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the b-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers.",
keywords = "Arsenic, Lung development, Microarray, Protein array",
author = "Petrick, {Jay S.} and Blachere, {Francoise M.} and Ornella Selmin and Lantz, {Robert Clark}",
year = "2009",
month = "5",
doi = "10.1002/mnfr.200800019",
language = "English (US)",
volume = "53",
pages = "583--591",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "5",

}

TY - JOUR

T1 - Inorganic arsenic as a developmental toxicant

T2 - In utero exposure and alterations in the developing rat lungs

AU - Petrick, Jay S.

AU - Blachere, Francoise M.

AU - Selmin, Ornella

AU - Lantz, Robert Clark

PY - 2009/5

Y1 - 2009/5

N2 - In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the b-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers.

AB - In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the b-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers.

KW - Arsenic

KW - Lung development

KW - Microarray

KW - Protein array

UR - http://www.scopus.com/inward/record.url?scp=67649097384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649097384&partnerID=8YFLogxK

U2 - 10.1002/mnfr.200800019

DO - 10.1002/mnfr.200800019

M3 - Article

C2 - 19072884

AN - SCOPUS:67649097384

VL - 53

SP - 583

EP - 591

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - 5

ER -