Genotoxic effects of tacrolimus on human lymphocyte cells

Abstract

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 aber ration (CAs), micronuclei tests (MN) and cell growth kinetics such as mitotic index (MI) and replication index (RI) in human lymphocytes. The ceils were treated with 5, 25, 50, and 100 ng/ml concentrations of tac rolimus, for 24 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 concentration for 24 h and at 25 and 100 ng/ml for 48 h. Tacrolimus decreased MI at all concentrations (except 5 ng/ml) for all treatment periods. It also inhibited the RI at 50 and 100 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.

Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

“…4) reinforced these data. Our data obtained with FK-506 also corroborated those of Kurtoglu and Yuksel (2012) that did not find decrease of NDI in lymphocytes treated with concentrations of 5, 25 and 50 ng/ml of FK-506. These authors observed a decrease of the NDI in cells treated with the concentration of 100 ng/ml, that is extremely high and not observed clinically.…”

“…Mutagenic effect of FK-506 was demonstrated in cultures of human lymphocytes by Kurtoglu and Yuksel (2012) in concentrations ranging from 5 to 100 ng/ml and by Oliveira et al (2004) in concentrations ranging from 5 to 40 ng/ml. However, MRC-5 cells seems to be less sensitive to FK-506 since in our study mutagenic effects were observed only in concentrations higher than 24 ng/ml.…”

Genotoxic and cytotoxic effects of the novel immunosuppressive agent 3-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-4-methyl-1,2,4-triazole (MNITMT) on mouse bone marrow cells

“…Genotoxic effects were reported with immunosuppressive drugs. Tacrolimus (FK-506), a potent immunosuppressive drug, induced chromosomal aberrations (CA) and MN frequency at all concentrations for 24 and 48 h (Kurtoglu and Yuksel 2012). Similar results were reported by others (Oliveira et al 2004), who found that cultures supplemented with the immunosuppressive drugs mycophenolate mofetil and tacrolimus showed higher amounts of micronuclei compared to controls in all concentrations tested.…”

Protective effect of extracts of Teucrium Polium and Rumex Crispus against cyclophosphamide-induced genotoxic damage in human lymphocytes

“…Genotoxic substances induce damage in cells through interaction with the DNA and can result, including single-and double-strand breaks, cross-links between DNA bases and proteins, and chemical additions to the DNA. The occurrence of genomic damage, if left unrepaired, may result in the formation of DNA adducts, chromosome/chromatid breaks, or aneuploidy and is associated with the formation of micronucleus (MN), sister chromatid exchange (SCE), and overall genomic instability [17,26]. This may be the reason for SCE and MN formation in lymphocyte cells after CP treatment.…”