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- Title
P-TA/07- CELL PROLIFERATION INDUCTION IN HUMAN BREAST CANCER CELL LINES MEDIATED BY ARYL HYDROCARBON RECEPTOR AFTER 14 DAYS CHLORPYRIFOS EXPOSURE.
- Authors
Moyano, P.; Del Pino, J.; Muñoz-Calero, P.; Pelayo, A.; García, J. M.; Lobo, M.; García, J.; Frejo, M. T.
- Abstract
Animal studies show that CPF induces breast cancer after long term exposure. In addition, epidemiological studies suggested a higher risk of breast cancer after long term chlorpyrifos (CPF) exposure. Moreover, previous in vitro studies described that CPF induced cell proliferation in human MCF-7 (hormone-dependent cells), but not in MDA-MB-231 (no hormone-dependent cells) breast cancer cell lines. These studies show that CPF mediated, in part, this effect through estrogen receptor (ER) in MCF-7 cells. However, animal studies showed that CPF decreases ER after long term exposure, and CPF has been shown to be a weak ER agonist, so this mechanism could not be involved after long term exposure. Otherwise, CPF has been also reported to be an agonist of aryl hydrocarbon receptors (AhR) and the treatment of AhR agonist in these cell lines has been shown to induce cell proliferation, so this mechanism could mediate this effect. Finally, the studies developed were performed only with CPF, but not with its toxic metabolite, chlorpyrifos oxon (CPFO), which may lead to other possible results with CPFO. The present study examined the effects of CPF and CPFO after 14 days exposure on the growth of MCF-7 and MDA-MB-231 cell lines through ER and AhR. The results showed that CPF and CPFO increased, concentration-dependently, cell proliferation of MCF-7 and MDA-MB-231 cells in phenol- and estrogen-free conditions. This increasing trend was bigger after CPFO exposure than after CPF exposure in both cell lines. This effect is supported by previous studies and could be explained through the bigger toxicity of CPFO. The observed effect was reversed by CPF or CPFO co-treatment only with CH-223191 (AhR antagonist) in MCF-7 cells and MDA-MB-231 cells, but not after CPF or CPFO co-treatment with tamoxifen (ER antagonist) in MCF-7 cells. These results indicate that only aryl hydrocarbon receptors are involved with the induction of cell proliferation in MCF-7 and MDA-MB-231 cells after 14 days exposure to CPF or CPFO. Our present results provide new understanding of the mechanisms contributing to the harmful effects of CPF and CPFO, and its possible relevance in the pathogenesis of breast cancer after long term exposure.
- Publication
Revista de Toxicología, 2019, Vol 36, Issue 1, p80
- ISSN
0212-7113
- Publication type
Article