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.
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.
Jin
Bohwan
B
College of Veterinary Medicine, Seoul National University, San 56-1, Sinlimdong, Kwanakgu, Seoul 151-742, South Korea.
Kim
Gyongsun
G
Park
Duk Woong
DW
Ryu
Doug-Young
DY
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
D000072317:Polychlorinated Dibenzodioxins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine