Early effects of cyclosporin A on in vivo oncogene expression

Cyclosporine is a widely used immunosuppressant drug, but development of secondary malignancies has been observed after Cyclosporine containing treatments. In our study we investigated the early effect of Cyclosporin A on oncogene expression. 6, 12, 18 and 24 hours after 80 mg/bwkg Cydosporin A treatment, RNA was isolated from different organs, slot blotted onto Hybond N+ membrane and hybridized with chemiluminescently labelled oncogene probes. As a positive control, rehybridisation with beta-actin probe was used. X-ray films were exposed for 15 minutes, developed, evaluated with densitometer, and the results were expressed as a ratio to the positive control. There was no effect of Cyclosporine A on the expression of c-sis and il-2 receptor genes. The expression of N-ras, c-myc, c-ptc/ret and c-myb oncogenes was elevated in the thymus, lymph nodes, spleen and liver, either transitionally or continuously. We could not detect any elevated gene expressions in the kidney, lung and bone marrow.