The transcriptional signature of dioxin in human hepatoma HepG2 cells
Section snippets
Cells, growth conditions, and treatments
Human hepatoma HepG2 cells were grown to 80% confluence in alpha minimal essential medium (α-MEM) (GIBCO BRL Life Technologies) containing 10% fetal bovine serum and 1% antibiotics. Four sets of experimental conditions were analyzed. One set consisted of cells treated for 8 hr with 10 nM TCDD dissolved in methanol; the second set was a control for the previous one and was treated with the same concentration of methanol as the TCDD-treated set. A third set received 20 μg/mL of CX 1 hr prior to
Results and discussion
Treatment of HepG2 cells with 10 nM TCDD resulted in gene expression changes in 310 genes from a total of 5686 annotated gene sequences and an additional 400 ESTs from 2949 unannotated sequences; only 4076 PCR products on the slide gave fluorescent signals that met the inclusion criteria (see the Materials and Methods Section), suggesting that many of the genes included in the array might not be expressed in HepG2 cells. Of the known genes, 114 were up-regulated and 196 down-regulated. Thirty
Conclusions
Functional clustering of genes regulated by TCDD reveals multiple physiological interactions that might explain many of the biological consequences of TCDD exposure, yet no unambiguous picture emerges from these results. For example, in most cases in which cellular processes such as apoptosis or angiogenesis are involved, some of the different genes with related roles are induced, whereas others are repressed with no apparent underlying rationale. Furthermore, although the majority of genes
Acknowledgements
We thank Bruce Aronow (Children’s Hospital Research Foundation, Cincinnati) for help and advice on the use of the Incyte GemTools software. This work was supported by Grants NIEHS ES06273 and NIEHS P30 ES06096. A. M. was supported in part by a U.S. EPA STAR Fellowship Grant.
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