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 [1-3].

The object of this study was to assess the impact of CsA exposure (8 hours, early cell response) on expression of genes associated with DNA repair in human dermal fibroblasts (NHDF).

NHDF cells were obtained from Clonetics (San Diego, CA) and routinely maintained in FBM medium (Lonza, Basel, Switzerland). Using oligonucleotide microarray technique HG–U133A 2.0 (Affymetrix) we compared transcriptional activity of genes associated with DNA repair in NHDF after 8 hours of cells exposition to CsA (c=100 ng/ml) in relation to control cells.

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 38 probes (p-value < 0.05; Fold Change > 2.0), including: BRCA1, RAD51, TOP2A, EXO1, RRM2, CDK1, and FEN1.

The obtained results suggest that CsA can have a silencing effect on DNA repair genes. 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.

References:

1. Voskamp P, Bodmann CA, Koehl GE, Tensen CP, Bavinck JN, Willemze R, Geissler EK, de Gruijl FR. No acceleration of UV-induced skin carcinogenesis from evenly spread dietary intake of cyclosporine in contrast to oral bolus dosages. Transplantation. 2013; 96(10): 871-876.
2. Wimmer CD, Angele MK, Schwarz B, Pratschke S, Rentsch M, Khandoga A, Guba M, Jauch KW, Bruns C, Graeb C. Impact of cyclosporine versus tacrolimus on the incidence of de novo malignancy following liver transplantation: a single center experience with 609 patients. Transpl Int. 2013; 26(10): 999-1006.
3. Herman-Edelstein M, Rozen-Zvi B, Zingerman B, Lichtenberg S, Malachi T, Gafter U, Ori Y. Effect of immunosuppressive drugs on DNA repair in human peripheral blood mononuclear cells. Biomed Pharmacother. 2012; 66(2): 111-115.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/31041 must be provided.

1. Polyunsaturated fatty acids potentate cytotoxicity of cisplatin in A549 cells
2. The effects of 300 mT static magnetic field on IL-6 secretion in normal human colon myofibroblasts
3. Polyunsaturated fatty acids inhibit melanoma cell growth in vitro
4. Influence of troglitazone, sodium butyrate and 5-aminosalicylic acid on the chemokine ENA-78/CXCL5 secretion in the intestinal subepithelial myofibroblasts
5. Polyunsaturated fatty acids alter expression of genes encoding antioxidant enzymes in A549 cells exposed to doxorubicin