DNA methylation alterations in response to pesticide exposure in vitro

• Published in: Environmental and molecular mutagenesis Vol. 53; no. 7; pp. 542 - 549
• Main Authors: Zhang, Xiao, Wallace, Andrew D., Du, Pan, Kibbe, Warren A., Jafari, Nadereh, Xie, Hehuang, Lin, Simon, Baccarelli, Andrea, Soares, Marcelo Bento, Hou, Lifang
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2012; Wiley-Liss
• Subjects: Bayes Theorem; Biological and medical sciences; carcinogenesis; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cluster Analysis; Computational Biology; DNA Methylation - drug effects; DNA methylation alteration; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humans; In Vitro Techniques; K562 Cells; Medical sciences; Molecular and cellular biology; pesticide exposure; Pesticides - toxicity; Principal Component Analysis; Sequence Analysis, DNA; Toxicology; Toxicology; DNA methylation alteration; DNA; pesticide exposure; Pesticides; Genetics; Exposure; Methylation; Carcinogenesis; In vitro
• ISSN: 0893-6692; 1098-2280; 1098-2280
• DOI: 10.1002/em.21718

Although pesticides are subject to extensive carcinogenicity testing before regulatory approval, pesticide exposure has repeatedly been associated with various cancers. This suggests that pesticides may cause cancer via nonmutagenicity mechanisms. The present study provides evidence to support the hypothesis that pesticide‐induced cancer may be mediated in part by epigenetic mechanisms. We examined whether exposure to seven commonly used pesticides (i.e., fonofos, parathion, terbufos, chlorpyrifos, diazinon, malathion, and phorate) induces DNA methylation alterations in vitro. We conducted genome‐wide DNA methylation analyses on DNA samples obtained from the human hematopoietic K562 cell line exposed to ethanol (control) and several organophosphate pesticides (OPs) using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian‐adjusted t‐tests were used to identify differentially methylated gene promoter CpG sites. In this report, we present our results on three pesticides (fonofos, parathion, and terbufos) that clustered together based on principle component analysis and hierarchical clustering. These three pesticides induced similar methylation changes in the promoter regions of 712 genes, while also exhibiting their own OP‐specific methylation alterations. Functional analysis of methylation changes specific to each OP, or common to all three OPs, revealed that differential methylation was associated with numerous genes that are involved in carcinogenesis‐related processes. Our results provide experimental evidence that pesticides may modify gene promoter DNA methylation levels, suggesting that epigenetic mechanisms may contribute to pesticide‐induced carcinogenesis. Further studies in other cell types and human samples are required, as well as determining the impact of these methylation changes on gene expression. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.