Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 250, Issue 2, Pages 117-129Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2010.09.018
Keywords
Arsenic; Cadmium; Metabolism; Cell cycle; Toxicogenomics; NTD
Categories
Funding
- National Institute of Environmental Health Sciences (NIEHS) [U10 ES 11387, R01-ES10613]
- US Environmental Protection Agency (EPA)
- NIEHS University of Washington (UW) Center for Child Environmental Health Risks Research [R826886, 1PO1ES09601]
- NIEHS
- National Science Foundation (NSF) Pacific Northwest Center for Human Health and Ocean Studies [P50 ES012762, OCE-0434087]
- NIEHS UW Center for Ecogenetics and Environmental Health [5 P30 ES07033]
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Arsenic (As) and cadmium (Cd) are well-characterized teratogens in animal models inducing embryotoxicity and neural tube defects (NTDs) when exposed during neurulation. Toxicological research is needed to resolve the specific biological processes and associated molecular pathways underlying metal-induced toxicity during this timeframe in gestational development. In this study, we investigated the dose-dependent effects of As and Cd on gene expression in C57BL/6J mouse embryos exposed in utero during neurulation (GD8) to identify significantly altered genes and corresponding biological processes associated with embryotoxicity. We quantitatively examined the toxicogenomic dose response relationship at the gene level. Our results suggest that As and Cd induce dose-dependent gene expression alterations representing shared (cell cycle, response to UV, glutathione metabolism, RNA processing) and unique (alcohol/sugar metabolism) biological processes, which serve as robust indicators of metal-induced developmental toxicity and indicate underlying embryotoxic effects. Our observations also correlate well with previously identified impacts of As and Cd on specific genes associated with metal-induced toxicity (Cdknla, MO). In summary, we have identified in a quantitative manner As and Cd induced dose-dependent effects on gene expression in mouse embryos during a peak window of sensitivity to embryotoxicity and NTDs in the sensitive C57BL/6J strain. (C) 2010 Elsevier Inc. All rights reserved.
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