Exposure to arsenic at levels found inU.S. drinking water modifies expression in the mouse lung.
The mechanisms of action of drinking water arsenic in the lung and the threshold for biologic effects remain controversial. Our study utilizes Affymetrix 22,690 transcript oligonucleotide microarrays to assess the long-term effects of increasing doses of drinking water arsenic on expression levels in the mouse lung. Mice were exposed at levels commonly found in contaminated drinking water wells in the United States (0, 0.1, 1 ppb), as well as the 50 ppb former maximum contaminant level, for 5 weeks. The expression profiles revealed modification of a number of important signaling pathways, many with corroborating evidence of arsenic responsiveness. We observed statistically significant expression changes for transcripts involved in angiogenesis, lipid metabolism, oxygen transport, apoptosis, cell cycle, and immune response. Validation by reverse transcription-PCR and immunoblot assays confirmed expression changes for a subset of transcripts. These data identify arsenic-modified signaling pathways that will help guide investigations into mechanisms of arsenic's health effects and clarify the threshold for biologic effects and potential disease risk.
Andrew
Angeline S
AS
Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. angeline.andrew@dartmouth.edu
Bernardo
Viviane
V
Warnke
Linda A
LA
Davey
Jennifer C
JC
Hampton
Thomas
T
Mason
Rebecca A
RA
Thorpe
Jessica E
JE
Ihnat
Michael A
MA
Hamilton
Joshua W
JW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018053:Arsenites / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D007109:Immunity / Q000187:drug effects / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D017670:Sodium Compounds / Q000633:toxicity*; D013997:Time Factors; D014481:United States; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
D018053:Arsenites; D012333:RNA, Messenger; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; C017947:sodium arsenite; D010100:Oxygen