No cyclosporin-induced chromosomal aberrations in human peripheral blood lymphocytes in vitro.
Continuous in vitro treatment of human peripheral blood lymphocytes with cyclosporin A for 20 h and 44 h in the absence of metabolic activation decreased the mitotic index in a concentration-dependent way (MI about 35% at 50 micrograms/ml). In the presence of 10% S9 lymphocytes were exposed to cyclosporin A at concentrations which formed cloudy suspension, i.e., above 100 micrograms/ml. A 2 h treatment in the presence of metabolic activation showed a depression of the mitotic index at the 44 h fixation time only. Based upon results concerning the depression of the mitotic index, slides of the 5, 10, 25 and 50 micrograms/ml (-S9, 20 h and 44 h continuous treatment) and 5, 150, 250 and 300 micrograms/ml (+S9, 2 h pulse treatment) treatment groups were selected to be analyzed in the chromosomal aberration assay. At no concentration and at no fixation time did cyclosporin A increase the frequency of cells with chromosomal aberrations.
Zwanenburg
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Sandoz Pharma Ltd., Drug Safety Assessment, Toxicology, Basel, Switzerland.
Cordier
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A
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004355:Drug Stability; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008940:Mitotic Index; D051381:Rats
D016572:Cyclosporine