Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this
data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of
early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information
to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study
we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of
the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach.
Adult Muta™Mousemales were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive
days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and
protein analyseswere employed to characterize responses in the forestomach.Microarray results showed altered
expression of 414 genes across all treatment groups (+/-1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant
downregulation of genes associated with phase II xenobioticmetabolismand increased expression of genes implicated
in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation
were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially
expressed genes in the forestomach from the present study to differentially expressed genes identified in
human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed
significant commonalities between the two models. Our results provide molecular evidence supporting the use
of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans
| Référence | 2835 |
| Année | 2013 |
| Type | Article |
| Lien document | |
| Lien externe | http://www.sciencedirect.com/science/article/pii/S0041008X13002573 |
| Auteur | Labib S |
| Auteurs associés | Charles H. Guo, Andrew Williams, Carole L. Yauk, Paul A. White, Sabina Halappanavar |
| Discipline | Autres |
| Revue | Toxicol Appl Pharmacol. |
| Référence Revue | 273(2):269-80 |
