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Current Topics in Toxicology   Volumes    Volume 12 
DNA methylation of repeated elements and cancer-related genes in normal human liver, and in cancer and non-cancer liver cell lines, treated with 5adC or PCB126
D. Desaulniers, G.-H. Xiao, C. Cummings-Lorbetskie, L. Stubbert, C. Parfett
Pages: 47 - 74
Number of pages: 28
Current Topics in Toxicology
Volume 12 

Copyright © 2016 Research Trends. All rights reserved

DNA methylation is an important epigenetic mechanism contributing to the regulation of gene expression and to the stability of DNA repeated sequences. Abnormal DNA methylation is a characteristic of cancer cells and there are scientific concerns that exposure to environmental contaminants (EC) might contribute to carcinogenesis by altering DNA methylation mechanisms. This study compared DNA methylation of repeated elements and cancer-related genes in normal human liver, and in cancer (HepG2) and non-cancer (HC-04) cell lines, and investigated the effects of 5-aza-2ā€™-deoxycytidine (5adC; a demethylation control) and polychlorinated biphenyl-126 (PCB126), a non-genotoxic rodent hepatocarcinogen. The results revealed striking cell-type differences in DNA methylation of repeated elements (AluYb8, LINE-1, Sat-alpha) and 7/9 cancer-related genes (CCND2, DAB2IP, DLEC1, GSTp1, OPCML, RASSF1, RUNX3, but not SFRP2 and SOCS1). In 72-h dose-response experiments, 5adC induced ā€œUā€ shape demethylation responses in the nine investigated genes, but associated with elevated mRNA expression only in 6/9 and 3/9 genes in HC-04 and HepG2 cells, respectively. DNA methylation was resistant to PCB126 in most genes in both cell lines, except for reduced promoter methylation and increased expression of GSTp1 in HepG2 cells, which further support a role for oxidative stress in PCB126-induced oncogenesis/toxicity. Finally, the different DNA methylation patterns and gene expression responses between the non-cancer HC-04 and cancer HepG2 cell lines provide alternative models to further explore epigenetic divergence in gene expression regulation.
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