In vitro genotoxicity testing of the furylethylene derivative UC-245 in human cells

The possible genotoxic potential of the 2-furylethylene derivative UC-245 has been evaluated in vitro using human cells as a test system. This compound was synthesized at the Centro de Bioactivos Químicos, Universidad Central de Las Villas (Cuba) and it appears to be effective against leishmaniosis. The induced genetic damage was determined by scoring the frequency of micronuclei (MN) and the frequency of sister chromatid exchanges (SCE) in primary lymphocyte cultures set up from two different donors. The DNA breakage level was also evaluated by the Comet assay, using an established human lymphoblastoid cell line (TK6). For the MN and SCE studies, to detect eventual metabolic modification in the genotoxicity of this compound, the cultures were treated with S9 microsomal fraction. The results obtained indicate that, under the experimental conditions used, the test agent does not induce significant increases in the frequency of micronucleated cells, irrespective of presence/absence of the metabolic fraction, which would indicate a lack of clastogenic and/or aneugenic potential. Nevertheless, a clear and significant increase in the SCE frequency was observed in the treatments without S9. This would support the 2-furylethylene derivative UC-245 inducing DNA primary damage. In addition, the results obtained in the Comet assay also show that UC-245 induces a significant increase in the level of DNA breakage, which would confirm its genotoxicity.