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Toxicology. 2008 Feb 3;244(1):49-55. Epub 2007 Nov 12.

Effects of long-term low-dose cadmium exposure on genomic DNA methylation in human embryo lung fibroblast cells.

Author information

1
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

Abstract

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.

PMID:
18077075
DOI:
10.1016/j.tox.2007.10.028
[Indexed for MEDLINE]
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