Inorganic arsenic as a developmental toxicant: in utero exposure and alterations in the developing rat lungs.
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 beta-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.
Petrick
Jay S
JS
Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85724-5044, USA.
Blachere
Francoise M
FM
Selmin
Ornella
O
Lantz
Robert Clark
RC
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000187:drug effects*; D020869:Gene Expression Profiling; D015723:Gene Library; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D040081:Protein Array Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001151:Arsenic