| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2148208 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2012 | 8 Pages |
Although cadmium is a well-established human carcinogen, the mechanisms by which it induces cancer are poorly understood. It is suggested that cadmium-mediated carcinogenesis may include the modulation of gene expression and signal-transduction pathways, interference with antioxidant enzymes, inhibition of DNA repair and DNA methylation, and induction of apoptosis. Nevertheless, no predominant mechanism playing a role in metal-induced carcinogenesis has been reported. In the present study, we used a pig Robertsonian translocation model, which is a cross between a wild boar and domestic pig resulting in Robertsonian translocation (37,XX,der15;17 or 37,XY,der15;17), to determine the role of cadmium sulfate in the modulation of genomic DNA-methylation status and the induction of aneuploidy. We found a cadmium-mediated increase in aneuploidy within chromosome group A and C, but not within chromosome group D containing the translocated chromosome der15,17 which indicates that translocated chromosome is not more prone to chromosomal aberrations than are other chromosomes. We suggest that cadmium-induced aneuploidy (up to 5-μM concentration) may be mediated by global DNA hypermethylation as monitored with HPLC and 5-mdC immunostaining. In addition, the cyto- and genotoxic potential of cadmium was evaluated. Cadmium sulfate was able to induce apoptosis, inhibit cell-proliferative status and expression of nucleolar organizer regions (NORs), and increase oxidative DNA damage (8-oxoG content).
► Cadmium sulfate induces aneuploidy in pig lymphocytes containing the translocated chromosome der15,17. ► The increase in aneuploidy events was exclusively seen within sub- and metacentric chromosomes. ► Cadmium-induced aneuploidy may be mediated by global DNA hypermethylation. ► Cadmium also promotes apoptosis, reduces cell proliferative activity and expression of nucleolar organizer regions and stimulates oxidative DNA damage.
