Genotoxicity of pemetrexed in human peripheral blood lymphocytes.

摘要: Pemetrexed (PMX) is an antineoplastic antifolate used in the treatment of non-small cell lung cancer, mesothelioma and several types neoplasms. Its toxicity tumor cells has been linked with potent inhibition thymidylate synthase, dihydrofolate reductase glycinamide ribonucleotide formyl transferase, subsequent depletion both purine pyrimidine nucleotides. However, cytogenetic PMX non-diseased not adequately studied; despite increasing data on DNA-damaging potential agents normal cells. In present study, genotoxic was evaluated peripheral blood lymphocytes obtained from healthy human subjects using chromosome aberration (CA), sister chromatid exchange (SCE) micronucleus (MN) assays as damage markers. Human were exposed to four different concentrations (25, 50, 75 100 μg/mL) for 24- 48-h periods. significantly increased formation CA 24-h treatment, but treatment. did increase mean SCE frequency periods; however, there a striking (although statistically significant, p > 0.05) number SCEs at 25 μg/mL (24- treatment) 50 μg/mL (24-h due single-cell level. Interestingly, induce MN either or strongly decreased mitotic index (MI), proliferation (PI) nuclear division (NDI) Our results suggest that cytotoxic effect against which are reached vivo plasma.