The genotoxic effects of Tacrolimus

Tacrolimus, although fundamental drug of immunsuppressive treatment, have serious side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation such as skin cancer and lymphoma. In this study, possible genotoxic effects of Tacrolimus were evaluated on human lymphocyte chromosomes using chromosome aberrations (CA), sister chromatide exchanges (SCE), micronucleus (MN) and cell growth kinetics as parameters. The lymphocytes were exposed to four different concentrations of the Tacrolimus (5, 25, 50,100 ng/ml) for two different durations (24 and 48 h). Tacrolimus induced CAs at all concentrations for 24 and 48 h. Similary there was a significant increase in the frequency of total micronuclei in exposed groups as compared to control group. In additon, it induced the SCE at highest concantration (100 ng/ml) for 24 h and at 25 and 100 ng/ml for 48 h. Tacrolimus decreased mitotic index (MI) at all concentrations except 5 ng/ml for 24 and 48 h. It inhibited lymphocyte proliferation (RI) at all concentrations for 48 h and only 50 and 100 ng/ml for 24 h. It was concluded that Tacrolimus has potent mutagenity and it can cause genetic damage leading to a malignancy.Key Words: Tacrolimus, sister chromatide exchange, chromosome aberration, micronucleus, cell growth kinetics, genotoxicity