Influence of cyclosporin A on expression pattern of genes associated with dna repair in human dermal fibroblasts.
Cyclosporin A (CsA) is a cyclic nonribosomal peptide with immunosuppressive activity. Chronic immunosuppressive medication is associated with time distant side effects and is the cause of the different secondary diseases, including cancers (especially skin cancers). Anomalies in the functioning of DNA repair mechanisms are closely related to the processes of neoplastic transformation. The object of this study was to assess the impact of CsA exposure (8 h, early cell response) on expression of genes associated with DNA repair in normal human dermal fibroblasts (NHDF). NHDF from CC-2511 cell line were routinely maintained in FBM medium. Transcriptional activity of genes associated with DNA repair in NHDF after 8 h of cells exposition to CsA (C = 100 ng/mL) in relation to control cells was compared using Affymetrix HG-U133A 2.0 oligonucleotide microarray technique. GeneSpring GX fluorescence signals analysis of 1514 probes, which represented the expression of 875 genes selected from the NetAffx Analysis Center database for "DNA repair" query, demonstrated the inhibited expression of 32 probes (p-value < 0.05; Fold Change > 2.0), including: BRCA1, RAD51, TOP2A, EXO1, RRM2, CDK1 and POLE2. The obtained results suggest that CsA can have a silencing effect on DNA repair genes. Therefore, the risk of skin cancer development during CsA therapy can result not only from immunosuppressive effects of the drug, but is also likely to arise from inhibition of DNA repair pathways.
Grzegorz
G
Hibner
Alicja
A
Zajdel
Adam
A
Wilczok
D018929:Cell Culture Techniques; D002460:Cell Line; D016572:Cyclosporine / Q000009:adverse effects*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000187:drug effects* / Q000473:pathology
D007166:Immunosuppressive Agents; D016572:Cyclosporine