Effects of long-term low-dose cadmium exposure on genomic DNA methylation in human embryo lung fibroblast cells.
Cadmium is a toxic transition metal of continuing occupational and environmental concern. As a well-recognized human carcinogen, its carcinogenic mechanisms are still poorly understood. Cadmium has long been considered a non-genotoxic carcinogen and thought to act through epigenetic mechanisms. In the present study, we tested the effects of long-term low-dose cadmium exposure on DNA methylation in human embryo lung fibroblast (HLF) cells. After 2 months of exposure to 0-1.5 micromol/L cadmium, both the level of genomic DNA methylation and the enzyme activity of DNA methyltransferases (DNMTs) were increased in a concentration-related manner. Moreover, our results showed that cadmium exposure up-regulated the mRNA levels of DNMT1, DNMT3a and DNMT3b at higher concentrations. We further tested the growth dynamics of HLF cells, and observed significantly elevated growth rates, decreased cell population of G0/G1-phase and increased cell population of S-phase at 0.9, 1.2, and 1.5 micromol/L concentrations. Our study indicated that long-term low-dose cadmium exposure could disrupt DNA methylation, which may be one of the possible underlying carcinogenic mechanisms of cadmium.
Jiang
Gaofeng
G
Faculty of Preventive Medicine, Medical College, Wuhan University of Science and Technology, Huangjiahu Campus, Wuhan 430065, Hubei Province, People's Republic of China. jianggaofeng@yahoo.com.cn
Xu
Lei
L
Song
Shizhen
S
Zhu
Changcai
C
Wu
Qing
Q
Zhang
Ling
L
Wu
Lei
L
D000704:Analysis of Variance; D002104:Cadmium / Q000737:chemistry / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000196:embryology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000097584:DNA Methyltransferase 3B
D002104:Cadmium; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D012333:RNA, Messenger; D012097:Repressor Proteins; D000097584:DNA Methyltransferase 3B; C411744:DMAP1 protein, human; C000717967:DNMT3A protein, human