Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure

Environmental Health Perspectives
Jie LiuMichael P Waalkes

Abstract

Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of select...Continue Reading

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Citations

Nov 2, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jun ShenMichael P Waalkes
Jun 8, 2007·BMC Genomics·Veronique MalardEric Quemeneur
Aug 29, 2007·Tissue Engineering·Kristen A WieghausEdward A Botchwey
Jun 21, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jie Liu, Michael P Waalkes
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Methods Mentioned

BETA
chip
Feature Extraction
PCR
electrophoresis

Software Mentioned

Ingenuity
Rosetta Resolver system
Rosetta Resolver
Agilent Feature Extraction
ABI Primer Express
Ingenuity Pathway
Rosetta
Ingenuity Pathways Analysis

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