کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599966 1133243 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discriminating classes of developmental toxicants using gene expression profiling in the embryonic stem cell test
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Discriminating classes of developmental toxicants using gene expression profiling in the embryonic stem cell test
چکیده انگلیسی

The embryonic stem cell test (EST) has been shown to be a promising in vitro method for the prediction of developmental toxicity. In our previous studies, we demonstrated that the implementation of gene expression analysis in the EST may further improve the identification of developmental toxicants. In the present study, we investigated if gene expression profiling could be used to discriminate compound classes with distinct modes of action (MoA) using the EST protocol. Gene expression data of our previous study were used and were analyzed of embryonic stem cell (ESC) differentiation cultures exposed to six compounds belonging to two classes with distinct MoA, namely phthalates and triazoles. We used three approaches to study class-characteristic gene regulation that may be useful for discrimination of compound classes. First, at the individual gene level, gene signatures characteristic for each class were identified that successfully discriminated both classes using principal component analysis. Second, at the functional level, enriched gene ontology (GO) biological processes showed their usefulness for class discrimination via hierarchical clustering. Third, two previously identified gene sets, which we designed to predict developmental toxicity, appeared successful in separating phthalate from triazole compounds. In summary, we established the possibility to discriminate between compound classes in the EST system using three different specific transcriptomics-based approaches. Differential gene expression information specific for the class of compound under study may be employed to optimize prioritization of compounds within that class for further testing.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 201, Issue 2, 5 March 2011, Pages 143–151
نویسندگان
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