GENOTOXIC EFFECTS OF TACROLIMUS ON HUMAN LYMPHOCYTE CELLS

摘要

We designed in vitro study to determine possible genotoxic effects of tacrolimus (FK-506), which is used as a potent immunosuppressive drug, by using sister chromatid exchange (SCEs), chromosome aberration (CAs), micronuclei tests (MN) and cell growthkinetics such as mitotic index (Ml) and replication index (RI) in human lymphocytes. The cells were treated with 5, 25, 50, and 100 ng/mL concentrations of tacrolimus, for 24 h and 48 h treatment periods. Tacrolimus induced CA and MN frequency at all concentrations for 24 and 48 h In additon, it induced the SCE at the highest concantration for 24 h and at 25 and 100 ng/mL for 48 h. Tacrolimus decreased Ml at all concentrations (except 5 ng/mL) for all treatment periods. It also inhibited the Rl at 50 and 1.00 ng/mL concentrations for 24 h and at all concentrations for 48 h. Treatments given with tacrolimus result in the enhance of the different endpoints of genotoxicity, suggesting its mutagenic action on lymphocytes in vitro.