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- Title
P-TA/06- CHLORPYRIFOS-INDUCED CELL PROLIFERATION IN HUMAN BREAST CANCER CELL LINES MEDIATED BY ESTROGEN RECEPTOR AND ARYL HYDROCARBON RECEPTOR AFTER 24 h EXPOSURE.
- Authors
Moyano, P.; Del Pino, J.; Muñoz-Calero, P.; Pelayo, A.; García, J. M.; Lobo, M.; García, J.; Frejo, M. T.
- Abstract
Epidemiological studies suggest an association between chlorpyrifos (CPF) exposure and cancer risk. Animal studies show that CPF exposure induces breast cancer. Moreover, previous in vitro studies described that CPF induced cell proliferation in human MCF-7 (hormone-dependent cells), but not in human 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. 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 also mediate this effect. Finally, these studies were performed only with CPF, but not with its toxic metabolite, chlorpyrifos oxon (CPFO), which is mainly present in the body, suggesting other possible results could be observed with CPFO. The present study examined the effects of CPF and CPFO after 24 h exposure on the growth of MCF-7 and MDA-MB-231 cell lines through ER and AhR mechanims. The results showed that CPF and CPFO concentration-dependently increased 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 increase of cell proliferation was reversed by cotreatment with tamoxifen (ER antagonist) or CH-223191 (AhR antagonist) in MCF-7 cells, but was only reversed after CH-223191 co-treatment with CPF or CPFO in MDA-MB-231 cells. These results indicate that both receptors are involved with the induction of cell proliferation in MCF-7, but only AhR was involved in MDA-MB-231 cells after 24 h 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.
- Publication
Revista de Toxicología, 2019, Vol 36, Issue 1, p79
- ISSN
0212-7113
- Publication type
Article