A commercial formulation of glyphosate inhibits proliferation and differentiation to adipocytes and induces apoptosis in 3T3-L1 fibroblasts

Glyphosate-based herbicides are extensively used for weed control all over the world. Therefore, it is important to investigate the putative toxic effects of these formulations which include not only glyphosate itself but also surfactants that may also be toxic. 3T3-L1 fibroblasts are a useful tool...

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Autor principal: Martini, C.N
Otros Autores: Gabrielli, M., Vila, M.D.C
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2012
Acceso en línea:Registro en Scopus
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Registro en la Biblioteca Digital
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024 7 |2 scopus  |a 2-s2.0-84863842719 
024 7 |2 cas  |a caspase 3, 169592-56-7; glyphosate, 1071-83-6; lipocortin 5, 111237-10-6; Caspase 3, 3.4.22.-; Glycine, 56-40-6; Herbicides; glyphosate, 1071-83-6 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a TIVIE 
100 1 |a Martini, C.N. 
245 1 2 |a A commercial formulation of glyphosate inhibits proliferation and differentiation to adipocytes and induces apoptosis in 3T3-L1 fibroblasts 
260 |c 2012 
270 1 0 |m Vila, M.D.C.; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina; email: mvila@qb.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
504 |a Acquavella, J.F., Alexander, B.H., Mandel, J.S., Gustin, C., Baker, B., Chapman, P., Bleeke, M., Glyphosate biomonitoring for farmers and their families: results from the farm family exposure study (2004) Environ. Health Perspect., 112, pp. 321-326 
504 |a Benachour, N., Seralini, G.E., Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells (2009) Chem. Res. Toxicol., 22, pp. 97-105 
504 |a Benachour, N., Sipahutar, H., Moslemi, S., Gasnier, C., Travert, C., Seralini, G.E., Time- and dose-dependent effects of Roundup® on human embryonic and placental cells (2007) Arch. Environ. Contam. Toxicol., 53, pp. 126-133 
504 |a Bradford, M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye-binding (1976) Anal. Biochem., 72, pp. 248-254 
504 |a Dallegrave, E., Mantese, F.D., Oliveira, R.T., Andrade, A.J., Dalsenter, P.R., Langeloh, A., Pre- and postnatal toxicity of the commercial glyphosate formulation in Wistar rats (2007) Arch. Toxicol., 81, pp. 665-673 
504 |a De Roos, A.J., Blair, A., Rusiecki, J.A., Hoppin, J.A., Svec, M., Dosemeci, M., Sandler, D.P., Alavanja, M.C., Cancer incidence among glyphosate-exposed pesticide applicators in the agricultural health study (2005) Environ. Health Perspect., 113, pp. 49-54 
504 |a Dill, G.M., Cajacob, C.A., Padgette, S.R., Glyphosate-resistant crops: adoption, use and future considerations (2008) Pest Manag. Sci., 64, pp. 326-331 
504 |a Gianessi, L.P., Economic and herbicide use impacts of glyphosate-resistant crops (2005) Pest Manag. Sci., 61, pp. 241-245 
504 |a Jin, S., Zhai, B., Qiu, Z., Wu, J., Lane, M.D., Liao, K., C-Crk, a substrate of theinsulin-like growth factor-1 receptor tyrosine kinase, functions as an early signal mediator in the adipocyte differentiation process (2000) J. Biol. Chem., 275, pp. 34344-34352 
504 |a Liao, K., Lane, M.D., The blockade of preadipocyte differentiation by proteintyrosine phosphatase HA2 is reversed by vanadate (1995) J. Biol. Chem., 270, pp. 12123-12132 
504 |a Marc, J., Bellé, R., Morales, J., Cormier, P., Mulner-Lorillon, O., Formulated glyphosate activates the DNA-response checkpoint of the cell cycle leading to the prevention of G2/M transition (2004) Toxicol. Sci., 82, pp. 4364-4342 
504 |a Martini, C., Plaza, M.V., Vila, M.C., PKA-dependent and independent cAMP signalling in 3T3-L1 fibroblasts differentiation (2009) Mol. Cell. Endocrinol., 298, pp. 42-47 
504 |a Paganelli, A., Ganso, V., Acosta, H., López, S.L., Carrasco, A.E., Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling (2010) Chem. Res. Toxicol., 23, pp. 1586-1595 
504 |a Patel, Y.M., Lane, M.D., Mitotic clonal expansion during preadipocyte differentiation: calpain-mediated turnover of p27 (2000) J. Biol. Chem., 275, pp. 17653-17660 
504 |a Peruzzo, P.J., Porta, A.A., Ronco, A.E., Levels of glyphosate in surface waters, sediments and soils associated with direct sowing soybean cultivation in north pampasic region of Argentina (2008) Environ. Pollut., 156, pp. 61-66 
504 |a Poletta, G.L., Larriera, A., Kleinsorge, E., Mudry, M.D., Genotoxicity of the herbicide formulation Roundup (glyphosate) in broad-snouted caiman (Caiman latirostris) evidenced by the comet assay and the micronucleus test (2009) Mutat. Res., 672, pp. 95-102 
504 |a Qiu, Z., Wei, Y., Chen, N., Jiang, M., Wu, J., Liao, K., DNA synthesis and mitotic clonal expansion is not a required step for 3T3-L1 preadipocytes into adipocytes (2001) J. Biol. Chem., 276, pp. 11988-11995 
504 |a Richard, S., Moslemi, S., Sipahutar, H., Benachour, N., Seralini, G.E., Differential effects of glyphosate and roundup on human placental cells and aromatase (2005) Environ. Health Perspect., 113, pp. 716-720 
504 |a Rubin, C.S., Hirsch, A., Fung, C., Rosen, O.M., Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells (1978) J. Biol. Chem., 253, pp. 7570-7578 
504 |a Solomon, K.R., Anadón, A., Carrasquilla, G., Cerdeira, A.L., Marshall, J., Sanin, L.H., Coca and poppy eradication in Colombia: environmental and human health assessment of aerially applied glyphosate (2007) Rev. Environ. Contam. Toxicol., 190, pp. 43-125 
504 |a Student, A.K., Hsu, R.Y., Lane, M.D., Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes (1980) J. Biol. Chem., 255, pp. 4745-4750 
504 |a Yeh, W., Bierer, B.E., McKnight, S.L., Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells (1995) Proc. Natl Acad. Sci. USA, 92, pp. 11086-11090 
520 3 |a Glyphosate-based herbicides are extensively used for weed control all over the world. Therefore, it is important to investigate the putative toxic effects of these formulations which include not only glyphosate itself but also surfactants that may also be toxic. 3T3-L1 fibroblasts are a useful tool to study adipocyte differentiation, this cell line can be induced to differentiate by addition of a differentiation mixture containing insulin, dexamethasone and 3-isobutyl-1-methylxanthine. We used this cell line to investigate the effect of a commercial formulation of glyphosate (GF) on proliferation, survival and differentiation. It was found that treatment of exponentially growing cells with GF for 48. h inhibited proliferation in a dose-dependent manner. In addition, treatment with GF dilution 1:2000 during 24 or 48. h inhibited proliferation and increased cell death, as evaluated by trypan blue-exclusion, in a time-dependent manner. We showed that treatment of 3T3-L1 fibroblasts with GF increased caspase-3 like activity and annexin-V positive cells as evaluated by flow cytometric analysis, which are both indicative of induction of apoptosis. It was also found that after the removal of GF, remaining cells were able to restore proliferation. On the other hand, GF treatment severely inhibited the differentiation of 3T3-L1 fibroblasts to adipocytes. According to our results, a glyphosate-based herbicide inhibits proliferation and differentiation in this mammalian cell line and induces apoptosis suggesting GF-mediated cellular damage. Thus, GF is a potential risk factor for human health and the environment. © 2012 Elsevier Ltd.  |l eng 
593 |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina 
690 1 0 |a 3T3-L1 FIBROBLASTS 
690 1 0 |a APOPTOSIS 
690 1 0 |a DIFFERENTIATION 
690 1 0 |a GLYPHOSATE FORMULATION 
690 1 0 |a PROLIFERATION 
690 1 0 |a CASPASE 3 
690 1 0 |a GLYPHOSATE 
690 1 0 |a LIPOCORTIN 5 
690 1 0 |a ADIPOCYTE 
690 1 0 |a ANTIPROLIFERATIVE ACTIVITY 
690 1 0 |a APOPTOSIS 
690 1 0 |a ARTICLE 
690 1 0 |a CELL DAMAGE 
690 1 0 |a CELL DEATH 
690 1 0 |a CELL DIFFERENTIATION 
690 1 0 |a CELL SURVIVAL 
690 1 0 |a CONCENTRATION RESPONSE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a CYTOTOXICITY 
690 1 0 |a ENZYME ACTIVITY 
690 1 0 |a FIBROBLAST 
690 1 0 |a FLOW CYTOMETRY 
690 1 0 |a MAMMAL CELL 
690 1 0 |a 3T3 CELLS 
690 1 0 |a ADIPOCYTES 
690 1 0 |a ANIMALS 
690 1 0 |a APOPTOSIS 
690 1 0 |a CASPASE 3 
690 1 0 |a CELL DIFFERENTIATION 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a CELL SURVIVAL 
690 1 0 |a FIBROBLASTS 
690 1 0 |a GLYCINE 
690 1 0 |a HERBICIDES 
690 1 0 |a MICE 
690 1 0 |a MAMMALIA 
700 1 |a Gabrielli, M. 
700 1 |a Vila, M.D.C. 
773 0 |d 2012  |g v. 26  |h pp. 1007-1013  |k n. 6  |p Toxicol. Vitro  |x 08872333  |w (AR-BaUEN)CENRE-7046  |t Toxicology in Vitro 
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