Microarray analysis of gene regulation in the Hepa1c1c7 cell line following exposure to the DNA methylation inhibitor 5-aza-2(')-deoxycytidine and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

摘要

Differential expression of various genes was observed in the Hepa1c1c7 cell line following exposure to the DNA methylation inhibitor 5-aza-2(')-deoxycytidine (AzaC) and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AzaC treatment generally affected genes induced by TCDD by modulating their induction levels. Induction of several genes, such as receptor (calcitonin) activity modifying protein 3 (Ramp3) by TCDD was enhanced by AzaC, although AzaC by itself was without effect. Some genes, such as frequently rearranged in advanced T-cell lymphomas (Frat1), were up-regulated by AzaC alone, with this induction being negatively affected by TCDD. Other genes were induced by AzaC, TCDD and their co-treatment. In contrast, many genes such as small proline-rich protein 1A (Sprr1a) and 2A (Sprr1a) were up-regulated by AzaC, but not significantly affected by TCDD. In addition, a group of genes was down-regulated by AzaC, TCDD and their co-treatment. These findings suggest the TCDD-dependent regulation of various genes to be influenced by cellular DNA methylation status.