Evaluation of the cyto/genotoxicity profile of oxime K048 using human peripheral blood lymphocytes: An introductory study

•K048 is a model of perspective oxime against organophosphates poisoning.•K048 (730, 200, and 7.3 nM) did not influence lymphocytes viability.•The tested concentrations of K048 exhibited acceptable genotoxicity.

This study investigates the effects of oxime K048 (730, 200, and 7.3 nM) on the viability and chromosome stability of human peripheral blood lymphocytes (PBLs) after a 30 min exposure in vitro. Cytotoxicity was tested by a viability assay with ethidium bromide and acridine orange. For the evaluation of the genotoxic potential, we used comet assays, cytokinesis-blocked micronucleus (CBMN) assay, and chromosome aberration (CA) analysis. We found acceptable cytotoxicity for K048 (9.7 ± 2.1% non-viable PBL at highest concentration vs. 7.3 ± 2.5% in control; apoptosis dominated over necrosis). Overall primary DNA damage was low and not significantly different from controls. The hOGG1-comet assay showed a slight increase in the level of oxidative DNA damage. In oxime treated PBLs, we found 13-19 MN compared to 15 MN in control cultures. The frequencies and types of CA in oxime-treated PBLs did not significantly differ from controls. K048 showed acceptable biocompatibility at the level of cell viability and chromatin/chromosome integrity. Since no increase in secondary genome damage was detected, the primary DNA lesions may have resulted from treatment-induced cell stress, subsequently becoming repaired and not fixed as chromosome aberrations. The toxicity profile of K048 should be further studied and compared with other clinically relevant oximes.