title: Effects of long-term low-dose formaldehyde exposure on global genomic hypomethylation in 16HBE cells.
abstract: Formaldehyde (FA), a volatile organic compound, is a ubiquitous air pollutant that is classified as 'Carcinogenic to humans (Group 1)' by IARC (2006). As a well-recognized human carcinogen, its carcinogenic mechanisms are still poorly understood. Previous studies have emphasized on genetic changes. However, little is known about the epigenetic mechanisms of FA exposure. In this study, We not only characterized the epigenomic response to long-term low-dose FA exposure in 16HBE cells, but also examined the expression of DNA methyltransferases (DNMTs) and the methyl-CpG-binding protein DNA-binding domain protein 2 (MBD2). Each week the 16HBE cells were treated with 10 μM FA for 24 h (h). After 24 weeks (W) of exposure to FA, the level of genomic DNA methylation gradually decreased in a time-related manner. Moreover, our results showed that FA exposure down-regulated the expression of DNMT3a and DNMT3b at both mRNA and protein level, and up-regulated the levels of DNMT1 and MBD2 at both mRNA and protein level. Our study indicated that long-term FA exposure could disrupt genomic DNA methylation, which may be one of the possible underlying carcinogenic mechanisms of FA.
authors: School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, PR China. liuqingcheng222@yahoo.com.cn
authors: Qingcheng
authors: Q
authors: Liu
authors: Linqing
authors: L
authors: Yang
authors: Chunmei
authors: C
authors: Gong
authors: Gonghua
authors: G
authors: Tao
authors: Haiyan
authors: H
authors: Huang
authors: Jianjun
authors: J
authors: Liu
authors: Huimin
authors: H
authors: Zhang
authors: Desheng
authors: D
authors: Wu
authors: Bo
authors: B
authors: Xia
authors: Gonghua
authors: G
authors: Hu
authors: Kunpeng
authors: K
authors: Wang
authors: Zhixiong
authors: Z
authors: Zhuang
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019075:Electrophoresis, Capillary; D019084:Fluorescent Antibody Technique, Indirect; D005557:Formaldehyde / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C489325:MBD2 protein, human; D009153:Mutagens; D012333:RNA, Messenger; D005557:Formaldehyde; D044503:5-Methylcytosine; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases