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

Toxicology. 2008 Feb 3;244(1):49-55. doi: 10.1016/j.tox.2007.10.028. Epub 2007 Nov 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Cadmium / chemistry
  • Cadmium / toxicity*
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation / drug effects*
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Dose-Response Relationship, Drug
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Humans
  • Interphase / drug effects
  • Lung / cytology
  • Lung / embryology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • DMAP1 protein, human
  • DNMT3A protein, human
  • RNA, Messenger
  • Repressor Proteins
  • Cadmium
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A