Growth inhibition by cyclosporine A in vivo and in vitro.
Cyclosporine A is a commonly used immunosuppressant in organ transplant. However, in addition to its nephro- and hepato-toxicity, we now report that it also exerts growth inhibiting effects in vivo and in vitro. Rats treated with daily Cyclosporine A I.P. injections of 10 mg or 20 mg/kg body weight gained weight at significantly lower rates than controls over a six week period. This growth retardation was completely reversible. By 6 weeks post treatment, the body weights of the treated animals were the same as controls. In contrast, rats treated with lower doses of cyclosporine A (5 mg/kg) did not suffer any growth retardation throughout. In vitro, rat primary cultured fibroblasts treated with greater than 1 microgram/ml Cyclosporine A suffered 25-60% cell loss in the post-log phase but the cytotoxic effect was not apparent during the log phase of growth. Fibroblasts treated with less than or equal to 1 microgram/ml of Cyclosporine A did not suffer any cell loss. In conclusion, Cyclosporine A exerts growth inhibitory effects in vivo when given at greater than 5 mg/kg body weight and cytotoxic effects in vitro at greater than 1 microgram/ml.
Bennett
V J
VJ
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Detmar
J
J
Chang
P L
PL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006128:Growth / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins