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 of p,p′-DDE to affect myeloid cells. The aim of this study was to determine the effect of p,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. The p,p′-DDE effect on Ca2 i, C/EBPβ protein levels, PKCα and p38 activation, and the role of oxidative stress or PLA2 was assayed. Exposure to 1.9 μg/mL of p,p′-DDE increased Ca2 i, PKCα, p38, and C/EBPβ protein levels; the increase of nuclear C/EBPβ protein was dependent on p38. PKCα phosphorylation was dependent on PLA2 and p,p′-DDE-induced oxidative stress. p38 phosphorylation induced by p,p′-DDE was dependent on PLA2, PKC activation, and oxidative stress. These effects of p,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 to p,p′-DDE on the development of bone marrow disorders in humans, these effects deserve further study. © 2016 Nallely A. Torres-Avilés et al.
• 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 of p,p′-DDE to affect myeloid cells. The aim of this study was to determine the effect of p,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. The p,p′-DDE effect on Ca2%2bi, C/EBPβ protein levels, PKCα and p38 activation, and the role of oxidative stress or PLA2 was assayed. Exposure to 1.9 μg/mL of p,p′-DDE increased Ca2%2bi, PKCα, p38, and C/EBPβ protein levels; the increase of nuclear C/EBPβ protein was dependent on p38. PKCα phosphorylation was dependent on PLA2 and p,p′-DDE-induced oxidative stress. p38 phosphorylation induced by p,p′-DDE was dependent on PLA2, PKC activation, and oxidative stress. These effects of p,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 to p,p′-DDE on the development of bone marrow disorders in humans, these effects deserve further study. © 2016 Nallely A. Torres-Avilés et al.

authors

• Albores-Garciá D.
• Calderón-Aranda E.
• Luna A.L.
• Moreno-Galván M.
• Portales Pérez Diana Patricia
• Salgado Bustamante Mariana
• Torres-Avilés N.A.

publication date

• 2016-01-01

published in

• BioMed Research International  Journal

keywords

• 1,1 dichloro 2,2 bis(4 chlorophenyl)ethylene; calcium ion; CCAAT enhancer binding protein beta; mitogen activated protein kinase p38; protein kinase C alpha; 1,1 dichloro 2,2 bis(4 chlorophenyl)ethylene; calcium; CCAAT enhancer binding protein beta; CEBPB protein, human; protein kinase C alpha; Article; bone marrow; bone marrow cell; cell differentiation; controlled study; enzyme phosphorylation; HL 60 cell line; human; human cell; oxidative stress; risk; cell line; drug effects; HL-60 cell line; metabolism; signal transduction; Bone Marrow; Calcium; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Cell Line; Dichlorodiphenyl Dichloroethylene; HL-60 Cells; Humans; MAP Kinase Signaling System; Myeloid Cells; Oxidative Stress; Protein Kinase C-alpha

Digital Object Identifier (DOI)

• 10.1155/2016/1375606

PubMed ID

• 27833915

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volume

• 2016