Mechanisms of p,p'-DDE-induced apoptosis in human peripheral blood mononuclear cells.
p,p'-Dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of organochlorine insecticide p,p'-dichlorodiphenyltrichloroethane (DDT), has been detected in human populations living in malaria-endemic areas of México where this insecticide was used. DDE induces apoptosis in peripheral blood mononuclear cells (PMBC); however, the molecular mechanism of cell death induced by this compound is poorly understood. In the present study, PBMC isolated from healthy individuals (not exposed to DDE) were incubated in the presence of increasing concentrations of p,p'-DDE (0-80 microg/ml) over time. When PBMC were treated with low p,p'-DDE concentration (10 microg/ml) an antioxidant response and biomarkers of inflammation were induced, indicating a pro-inflammatory state. Moreover, when PBMC were treated with high p,p'-DDE concentration (80 microg/ml) several apoptotic biochemical events were triggered, such as activation of caspase-8, Bid, caspase-9 and caspase-3, as well as degradation of PARP and ubiquitination. The results described in this study show a possible inflammatory condition and the involvement of both extrinsic and intrinsic pathways in the induction of apoptosis in DDE-treated PBMC.
Alegría-Torres
Jorge A
JA
Departamento de Toxicología Ambiental, Facultad de Medicina, Universidad Autónoma de San Luís Potosí, 78210 San Luís Potosí, Mexico.
Díaz-Barriga
Fernando
F
Gandolfi
A Jay
AJ
Pérez-Maldonado
Iván N
IN
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects; D055815:Young Adult
D051023:BH3 Interacting Domain Death Agonist Protein; D015415:Biomarkers; D007306:Insecticides; D003633:Dichlorodiphenyl Dichloroethylene; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases