Trichloroethylene-Induced DNA Methylation Changes in Male F344 Rat Liver.
Trichloroethylene (TCE), a common environmental contaminant, causes hepatocellular carcinoma in mice but not in rats. To understand the mechanisms of the species-specific hepatocarcinogenecity of TCE, we examined the methylation status of DNA in the liver of rats exposed to TCE at 0 or 1000 mg/kg b.w. for 5 days using MeDIP-chip, bisulfite sequencing, COBRA, and LC-MS/MS. The related mRNA expression levels were measured by qPCR. Although no global DNA methylation change was detected, 806 genes were hypermethylated and 186 genes were hypomethylated. The genes with hypermethylated DNA were enriched in endocytosis, MAPK, and cAMP signaling pathways. We further confirmed the hypermethylation of Uhrf2 DNA and the hypomethylation of Hadhb DNA, which were negatively correlated with their mRNA expression levels. The transcriptional levels of Jun, Ihh, and Tet2 were significantly downregulated, whereas Cdkn1a was overexpressed. No mRNA expression change was found for Mki67, Myc, Uhrf1, and Dnmt1. In conclusion, TCE-induced DNA methylation changes in rats appear to suppress instead of promote hepatocarcinogenesis, which might play a role in the species-specific hepatocarcinogenecity of TCE.
Department of Physiology, School of Biology and Basic Medical Sciences, ‡Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, §Department of Toxicology, School of Public Health, Soochow University , Suzhou 215123, China.
Yan
Y
Jiang
Department of Physiology, School of Biology and Basic Medical Sciences, ‡Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, §Department of Toxicology, School of Public Health, Soochow University , Suzhou 215123, China.
Jiahong
J
Chen
Department of Physiology, School of Biology and Basic Medical Sciences, ‡Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, §Department of Toxicology, School of Public Health, Soochow University , Suzhou 215123, China.
Cong
C
Yue
Department of Physiology, School of Biology and Basic Medical Sciences, ‡Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, §Department of Toxicology, School of Public Health, Soochow University , Suzhou 215123, China.
Hang
H
Zhang
Department of Physiology, School of Biology and Basic Medical Sciences, ‡Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, §Department of Toxicology, School of Public Health, Soochow University , Suzhou 215123, China.
Tao
T
Chen
D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014241:Trichloroethylene / Q000008:administration & dosage / Q000633:toxicity*
D014241:Trichloroethylene; D004247:DNA