Arsenic- and cadmium-induced toxicogenomic response in mouse embryos undergoing neurulation.
Toxicol Appl Pharmacol
; 250(2): 117-29, 2011 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-20883709
ABSTRACT
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 (Cdkn1a, Mt1). 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arseniatos
/
Regulação da Expressão Gênica no Desenvolvimento
/
Cloreto de Cádmio
/
Toxicogenética
/
Neurulação
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos