Cadmium-induced changes in genomic DNA-methylation status increase aneuploidy events in a pig Robertsonian translocation model.

Abstract

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).

• Authors: Paulina Inglot, Anna Lewinska, Leszek Potocki, Bernadetta Oklejewicz, Anna Tabecka-Lonczynska, Marek Koziorowski, Monika Bugno-Poniewierska, Grzegorz Bartosz, Maciej Wnuk
• Journal: Mutation research (Mutat Res) Vol. 747 Issue 2 Pg. 182-9 (Sep 18 2012) ISSN: 0027-5107 [Print] Netherlands
• PMID: 22640880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Carcinogens
• Cadmium

Topics

• Aneuploidy
• Animals
• Apoptosis (drug effects)
• Cadmium (toxicity)
• Carcinogens (toxicity)
• Cell Proliferation (drug effects)
• DNA Methylation (drug effects)
• Hybridization, Genetic
• Karyotype
• Models, Animal
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Sus scrofa
• Translocation, Genetic