Effect of a phthalimide pesticide on human peripheral blood lymphocytes in vitro: induction of DNA damage

Abstract

Introduction. Captan is a contact fungicide from the phthalimide class, used in agriculture to combat plant diseases. However, the question of its genotoxicity for humans remains open. Various studies examining the mutagenic activity of captan using different tests have yielded conflicting results. This study aims to investigate the potential of captan to induce DNA damage in human peripheral blood lymphocytes in vitro using single-cell alkaline gel electrophoresis. Material and methods. The DNA-damaging effect of captan (0; 2.5; 5.0; 10.0; 12.5 and 25 μg/ml) on lymphocytes of 26 donors was assessed with metabolic activation (+S9) and without it (–S9) using DNA comet analysis. Results. In the absence of metabolic activation, captan exhibited a pronounced genotoxic effect on cells. Statistically significant effects of captan was found on lymphocytes of all donors. The level of DNA-damaging effect on lymphocytes from 20 out of 26 donors depended on the concentration. The fold increase in the “%DNA in the tail of comets” indicator compared to the negative control at a concentration of 25 μg/ml varied in the range of 4,3–226 times. In the presence of the S9 mixture, weak but significant effects meeting the criteria for a positive response were detected only in three donors. Limitations. The genotoxicity of captan was studied only in vitro. Conclusion. Captan induces DNA damage in human peripheral blood lymphocytes in vitro in the absence of metabolic activation. Under conditions of metabolic activation, genotoxic effects were low. The levels of DNA damage in peripheral blood lymphocytes of different donors after exposure to captan varied markedly, indicating the necessity to consider individual sensitivity to genotoxicants when utilizing the DNA comet method to assess the potential mutagenic activity of chemicals.