The insecticides permethrin and chlorpyrifos show limited genotoxicity and no leukemogenic potential in human and murine hematopoietic stem progenitor cells

Abstract

Epidemiological and clinical studies have revealed that maternal exposure to pesticides-insecticides during pregnancy is associated with an increased risk of infant or childhood acute leukemia. The household insecticides permethrin and chlorpyrifos, which are members of the pyrethroid and organophosphate families of pesticides, respectively, have been associated with both the induction of MLL rearrangements (MLLr) and the development of infant acute leukemia. Despite the epidemiological association between insecticides and increased risk of leukemia, whether such insecticides act as topo isomerase II DNA-damaging poisons remains unknown and studies testing the biological plausibility of such an association are lacking. Here, we assessed the genotoxicity, induction of MLLr and leukemogenic potential of permethrin and chlorpyrifos by taking advantage of cutting- edge in vitro and in vivo models using prenatal, neonatal and adult hematopoietic stem and progenitor cells (HSPC). Our data suggest that the insecticides tested show no cytotoxicity, limited genotoxicity and no leukemogenic potential in human and murine HSPC in vitro and in vivo.