In vitro genotoxic effects of pemetrexed and cefixime as single-agent or combination form on human peripheral blood lymphocytes

The aim of this study was to investigate the genotoxic effects of pemetrexed (PMX) (an antifolate for the treatment of lung cancer and mesothelioma) and cefixime (CFX) (a cephalosporin antibiotic) separately or in combination on human peripheral lymphocytes by using sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronucleus (MN) tests. Cells were treated separately with 25, 50, 75, 100 µg/ml PMX; 900, 1600, 2300, 3000 µg/ml CFX and with their combinations at their half concentrations for 24 and 48 hr. In this study, PMX significantly increased the formation of CAs in 24-hr treatment period, but not in 48-hr treatment. PMX did not induce the formation of SCE or MN either in 24- or 48-hr treatment periods. On the other hand, PMX significantly decreased the MI, PI and NDI at all concentrations and treatment times. No significant increase was detected in CA or MN in cultures treated with CFX for both treatment times. Although CFX induced the SCE at the two concentrations (2300 and 3000 µg/ml) for 24-hr treatment; and at all concentrations for 48-hr, the detected increases were not significant when compared to control and solvent control. CFX significantly decreased the MI and PI at all concentrations and treatment times. Although not statistically significant when compared to controls (negative and solvent control), CFX induced a concentration-dependent decrease in the NDI for 48-hr treatment (r = -0,979, P < 0.05). Combinations of PMX+CFX were detected to be more cytotoxic as compared to their separate treatments, but not genotoxic, in human peripheral lymphocytes.