Exposure top,p′-DDE Induces Morphological Changes and Activation of the PKCα-p38-C/EBPβPathway in Human Promyelocytic HL-60 Cells

Abstract

Dichlorodiphenyldichloroethylene (p,p′-DDE), the most persistent metabolite of dichlorodiphenyltrichloroethane (DDT), is still present in the human population. Both are present in the bone marrow of patients with bone marrow disorders, but thus far there are no studies that assess the capability ofp,p′-DDE to affect myeloid cells. The aim of this study was to determine the effect ofp,p′-DDE on promyelocytic cell differentiation and intracellular pathways related to this event.p,p′-DDE induced morphological changes compatible with promyelocytic differentiation in a concentration-dependent manner. Thep,p′-DDE effect onCa2+i, C/EBPβprotein levels, PKCαand p38 activation, and the role of oxidative stress or PLA2 was assayed. Exposure to 1.9 μg/mL ofp,p′-DDE increasedCa2+i, PKCα, p38, and C/EBPβprotein levels; the increase of nuclear C/EBPβprotein was dependent on p38. PKCαphosphorylation was dependent on PLA2 andp,p′-DDE-induced oxidative stress. p38 phosphorylation induced byp,p′-DDE was dependent on PLA2, PKC activation, and oxidative stress. These effects ofp,p′-DDE at concentrations found in human bone marrow may induce alterations in immature myeloid cells and could affect their cellular homeostasis. In order to establish the risk from exposure top,p′-DDE on the development of bone marrow disorders in humans, these effects deserve further study.