DNA hypomethylation and oxidative stress-mediated increase in genomic instability in equine sarcoid-derived fibroblasts.
It is widely accepted that equine sarcoid disease, the most common skin associated neoplasm in equids, is induced by bovine papillomavirus (BPV-1). Although BPV-1 DNA has been found in almost all examined sarcoids so far, its detailed impact on the horse's host cell metabolism is largely unknown. We used equine fibroblast cell lines originating from sarcoid biopsies to study BPV-1-associated changes on DNA methylation status and oxidative stress parameters. Sarcoid-derived fibroblasts manifested increased proliferation in vitro, transcriptional rDNA activity (NORs expression) and DNA hypomethylation compared to control cells. Cells isolated from equine sarcoids suffered from oxidative stress: the expression of antioxidant enzymes was decreased and the superoxide production was increased. Moreover, increased ploidy, oxidative DNA damage and micronuclei formation was monitored in sarcoid cells. We postulate that both altered DNA methylation status and redox milieu may affect genomic stability in BPV-1-infected cells and in turn contribute to sarcoid pathology.
Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland.
Leszek
L
Potocki
Anna
A
Lewinska
Jolanta
J
Klukowska-Rötzler
Monika
M
Bugno-Poniewierska
Christoph
C
Koch
Kathrin
K
Mählmann
Josef
J
Janda
Maciej
M
Wnuk
D000818:Animals; D017209:Apoptosis; D052688:Bovine papillomavirus 1 / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability / Q000235:genetics*; D006734:Horse Diseases / Q000473:pathology*; D006736:Horses; D018384:Oxidative Stress; D011003:Ploidies; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000473:pathology / Q000662:veterinary*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53