Effects of the organophosphate insecticides phosmet and chlorpyrifos on trophoblast JEG-3 cell death, proliferation and inflammatory molecule production

N GUIÑAZÚ, V, S GENTI-RAIMONDI, V RIVERO, GLADIS MAGNARELLI

TOXICOLOGY IN VITRO : AN INTERNATIONAL JOURNAL PUBLISHED IN ASSOCIATION WITH BIBRA.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 p. 406 - 413

0887-2333

Epidemiological data have associated environmental organophosphate insecticide (OP) exposure during 24pregnancy with fetal growth deficits. To better understand OP injury that may adversely affect preg- 25nancy, we used the JEG-3 choriocarcinoma cell line, which provide a recognized in vitro model to study 26placental function. The effects of the OP phosmet (Pm) and chlorpyrifos (Cp) on JEG-3 cells viability, pro- 27liferation, cell cycle and inflammatory molecule production were evaluated. Both insecticides affected 28cellular viability in a concentration- and time-dependent manner, inducing apoptosis and decreasing 29[3H]-thymidine incorporation. However, only Pm reduced DNA synthesis independently of cellular death 30and decreased the cell percentage at the S-phase. Unlike apoptosis, TNFa production varied with the con- 31centration tested, suggesting that other TNFa independent mechanisms might trigger cell death. No 32induction of the inflammatory molecule nitric oxide was detected. The mRNA levels of pro-inflammatory 33IL-6, IL-17 and the anti-inflammatory IL-13 cytokines were differentially modulated. These findings show 34that Pm and Cp generate a specific toxicity signature, altering cell viability and inducing an inflammatory 35cytokine profile, suggesting that trophoblasts may represent a possible target for OP adverse effects.