AI Article Synopsis
- - Cyclosporin A (CsA) is an immunosuppressive drug that can lead to serious long-term effects, including an increased risk of cancers, particularly skin cancers, due to impaired DNA repair mechanisms.
- - This study investigated how an 8-hour exposure to CsA affects DNA repair gene expression in normal human dermal fibroblasts, using a specific microarray technique to compare gene activity between treated and control cells.
- - Results showed that CsA significantly inhibited the expression of 32 important DNA repair genes (like BRCA1 and RAD51), suggesting that the risk of skin cancer during CsA therapy may stem from both its immunosuppressive effects and the suppression of DNA repair processes.
Article Abstract
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.
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