Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells
Abstract
We have evaluated the toxicity of four glyphosate (G)-based herbicides in Roundup formulations, from 10(5) times dilutions, on three different human cell types. This dilution level is far below agricultural recommendations and corresponds to low levels of residues in food or feed. The formulations have been compared to G alone and with its main metabolite AMPA or with one known adjuvant of R formulations, POEA. HUVEC primary neonate umbilical cord vein cells have been tested with 293 embryonic kidney and JEG3 placental cell lines. All R formulations cause total cell death within 24 h, through an inhibition of the mitochondrial succinate dehydrogenase activity, and necrosis, by release of cytosolic adenylate kinase measuring membrane damage. They also induce apoptosis via activation of enzymatic caspases 3/7 activity. This is confirmed by characteristic DNA fragmentation, nuclear shrinkage (pyknosis), and nuclear fragmentation (karyorrhexis), which is demonstrated by DAPI in apoptotic round cells. G provokes only apoptosis, and HUVEC are 100 times more sensitive overall at this level. The deleterious effects are not proportional to G concentrations but rather depend on the nature of the adjuvants. AMPA and POEA separately and synergistically damage cell membranes like R but at different concentrations. Their mixtures are generally even more harmful with G. In conclusion, the R adjuvants like POEA change human cell permeability and amplify toxicity induced already by G, through apoptosis and necrosis. The real threshold of G toxicity must take into account the presence of adjuvants but also G metabolism and time-amplified effects or bioaccumulation. This should be discussed when analyzing the in vivo toxic actions of R. This work clearly confirms that the adjuvants in Roundup formulations are not inert. Moreover, the proprietary mixtures available on the market could cause cell damage and even death around residual levels to be expected, especially in food and feed derived from R formulation-treated crops.
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The ultrastructural findings are consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation inducing necrosis of hepatocytes and other cell lines.
“This is consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation inducing necrosis of hepatocytes, and other cell lines (Benachour and Seralini, 2009;Benachour et al., 2007;Gasnier et al., 2010;Peixoto, 2005).”
From RETRACTED: Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize (2012) · cites this paper as Benachour and Seralini, 2009
R concentrations in the range of 103 times below the MRL can induce endocrine disturbances in human cells and toxic effects thereafter.
“Indeed, it has been demonstrated that R concentrations in the range of 103 times below the MRL can induce endocrine disturbances in human cells [8] and toxic effects thereafter [9].”
From Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize (2014) · cites this paper as [9]
This is consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation, inducing necrosis of hepatocytes, and in other cell lines.
“This is consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation, inducing necrosis of hepatocytes, and in other cell lines [8,9,44,45].”
From Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize (2014) · cites this paper as [9]
Cites
1 retracted
Williams, G. M., Kroes, R., & Munro, I. C. (2000) · Regulatory Toxicology and Pharmacology · doi:10.1006/rtph.1999.1371 · Cited by 864 · see citing works
RetractedMosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
Rapid colorimetric assay for cell growth and survival
Denizot, F., & Lang, R. (1986) · Journal of Immunological Methods · doi:10.1016/0022-1759(86)90368-6 · Cited by 4,907 · see citing works
Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β
Kuiper, G. G. J. M., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., van der Burg, B., & Gustafsson, J.-Å. (1998) · Endocrinology · doi:10.1210/endo.139.10.6216 · Cited by 4,203 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Pathways of apoptotic and non-apoptotic death in tumour cells
Okada, H., & Mak, T. W. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1412 · Cited by 1,043 · see citing works
The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity
Crouch, S. P. M., Kozlowski, R., Slater, K. J., & Fletcher, J. (1993) · Journal of Immunological Methods · doi:10.1016/0022-1759(93)90011-u · Cited by 926 · see citing works
Cell death modalities: classification and pathophysiological implications
Galluzzi, L., Maiuri, M. C., Vitale, I., Zischka, H., Castedo, M., Zitvogel, L., & Kroemer, G. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402148 · Cited by 832 · see citing works
Differential effects of glyphosate and roundup on human placental cells and aromatase
Richard, S., Moslemi, S., Sipahutar, H., Benachour, N., & Seralini, G.-E. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7728 · Cited by 619 · see citing works
Self-citationTsui, M. T., & Chu, L. M. (2003) · Chemosphere · doi:10.1016/s0045-6535(03)00306-0 · Cited by 610 · see citing works
The Role of Caspases in Development, Immunity, and Apoptotic Signal Transduction
Łoś, M., Wesselborg, S., & Schulze‐Osthoff, K. (1999) · Immunity · doi:10.1016/s1074-7613(00)80062-x · Cited by 392 · see citing works
Unidentified Inert Ingredients in Pesticides: Implications for Human and Environmental Health
Cox, C. S., & Surgan, M. H. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.9374 · Cited by 370 · see citing works
Riss, T., & Moravec, R. A. (2004) · Assay and Drug Development Technologies · doi:10.1089/154065804322966315 · Cited by 370 · see citing works
Acquavella, J., Alexander, B. H., Mandel, J. S., Gustin, C., Baker, B. A., Chapman, P. S., & Bleeke, M. S. (2003) · Environmental Health Perspectives · doi:10.1289/ehp.6667 · Cited by 310 · see citing works
Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation
Peixoto, F. (2005) · Chemosphere · doi:10.1016/j.chemosphere.2005.03.044 · Cited by 259 · see citing works
Morphological and cytochemical determination of cell death by apoptosis
Taatjes, D. J., Sobel, B. E., & Budd, R. C. (2007) · Histochemistry and Cell Biology · doi:10.1007/s00418-007-0356-9 · Cited by 235 · see citing works
Time- and dose-dependent effects of Roundup on human embryonic and placental cells
Benachour, N., Sipahutar, H., Moslemi, S., Gasnier, C., Travert, C., & Séralini, G. E. (2007) · Archives of Environmental Contamination and Toxicology · doi:10.1007/s00244-006-0154-8 · Cited by 226 · see citing works
Self-citationMale Pesticide Exposure and Pregnancy Outcome
Savitz, D. A., Arbuckle, T. E., Kaczor, D., & Curtis, K. M. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009231 · Cited by 207 · see citing works
Chemical mixtures: considering the evolution of toxicology and chemical assessment
Monosson, E. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.6987 · Cited by 171 · see citing works
Pesticide Roundup Provokes Cell Division Dysfunction at the Level of CDK1/Cyclin B Activation
Marc, J., Mulner‐Lorillon, O., Boulben, S., Hureau, D., Durand, G., & Bellé, R. (2002) · Chemical Research in Toxicology · doi:10.1021/tx015543g · Cited by 131 · see citing works
Evidence for the induction of apoptosis by endosulfan in a human T-cell leukemic line
Kannan, K., Holcombe, R. F., Jain, S. K., et al. (2000) · Molecular and Cellular Biochemistry · doi:10.1023/a:1007080910396 · Cited by 130 · see citing works
Bénachour, N., Moslemi, S., Sipahutar, H., & Séralini, G. (2007) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2007.03.033 · Cited by 115 · see citing works
Self-citationHeterogeneity of Vascular Endothelial Cells in Normal and Disease States
Thorin, É. (1998) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(98)00005-9 · Cited by 112 · see citing works
Differential Regulation of the TRAIL Death Receptors DR4 and DR5 by the Signal Recognition Particle
Ren, Y., Wagner, K. W., Knee, D. A., Aza‐Blanc, P., Nasoff, M. S., & Deveraux, Q. L. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-03-0184 · Cited by 104 · see citing works
International issues on human health effects of exposure to chemical mixtures.
FERON, V. J., Cassee, F. R., Groten, J. P., van Vliet, P. W., & van Zorge, J. A. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s6893 · Cited by 99 · see citing works
Thomas, P. K., Cooper, J. A. D., King, R. H. M., Workman, J. M., Schapira, A. H. V., Goss-Sampson, M. A., & Muller, D. P. R. (1993) · PubMed · Cited by 93 · see citing works
Choi, W. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg149 · Cited by 90 · see citing works
Xiao, D., Li, M., Herman-Antosiewicz, A., et al. (2006) · Nutrition and Cancer · doi:10.1207/s15327914nc5501_12 · Cited by 87 · see citing works
Omezzine, A., Chater, S., Mauduit, C., Florin, A., Tabone, É., Chuzel, F., Bars, R., & Benahmed, M. (2003) · Endocrinology · doi:10.1210/en.2002-220692 · Cited by 82 · see citing works
Ghanem, A., Bados, P., Kerhoas, L., et al. (2007) · Analytical Chemistry · doi:10.1021/ac062195k · Cited by 74 · see citing works
Rathinasamy, K., & Panda, D. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05413.x · Cited by 73 · see citing works
A glyphosate-based pesticide impinges on transcription
Marc, J., Breton, M. L., Cormier, P., Morales, J., Bellé, R., & Mulner‐Lorillon, O. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.07.014 · Cited by 68 · see citing works
Letcher, R. J., van Holsteijn, I., Drenth, H., Norstrom, R. J., Bergman, Å., Safe, S. H., Pieters, R. H. H., & van den Berg, M. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8746 · Cited by 66 · see citing works
Liu, J. J., Wang, W., Dicker, D. T., & El‐Deiry, W. S. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.8.2133 · Cited by 58 · see citing works
Human Multidrug Transporter ABCG2, a Target for Sensitizing Drug Resistance in Cancer Chemotherapy
Xu, J., Peng, H., & Zhang, J. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707780059580 · Cited by 51 · see citing works
Studies on a new group of biodegradable surfactants for glyphosate
Haefs, R., Schmitz-Eiberger, M. A., Mainx, H. G., et al. (2002) · Pest Management Science · doi:10.1002/ps.539 · Cited by 44 · see citing works
Nuclear magnetic resonance tim ecourse studies of glyphosate metabolism by microbial soil isolates
Gard, J. K., Feng, P., & Hutton, W. (1997) · Xenobiotica · doi:10.1080/004982597240235 · Cited by 33 · see citing works
Bouffant, R. L., Cormier, P., Cueff, A., Bellé, R., & Mulner‐Lorillon, O. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7173-0 · Cited by 30 · see citing works
Annas, A., Granberg, A. L., & Brittebo, E. B. (2000) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2000.9054 · Cited by 29 · see citing works
Ryu, H., Emberley, J. K., Schlezinger, J. J., Allan, L. L., Na, S., & Sherr, D. H. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.014712 · Cited by 29 · see citing works
In vitro endothelial cell susceptibility to xenobiotics: Comparison of three cell types
L'Azou, B., Fernandez, P., Bareille, R., Bénéteau, M., Bourget, C., Cambar, J., & Bordenave, L. (2005) · Cell Biology and Toxicology · doi:10.1007/s10565-005-0172-8 · Cited by 28 · see citing works
Travert, C., Carreau, S., & Goff, D. L. (2006) · Reproductive Toxicology · doi:10.1016/j.reprotox.2006.05.006 · Cited by 27 · see citing works
Solovyan, V. T., & Keski‐Oja, J. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401618 · Cited by 26 · see citing works
Scatena, R., Messana, I., Martorana, G. E., et al. (2004) · BMB Reports · doi:10.5483/bmbrep.2004.37.4.454 · Cited by 23 · see citing works
Human ocular efects from self-reported exposures to Roundup® herbicides
Acquavella, J., Weber, J. A., Cullen, M. R., et al. (1999) · Human & Experimental Toxicology · doi:10.1191/096032799678847087 · Cited by 21 · see citing works
TAKAHASHI, K., Horie, M., & Nobuji, A. O. B. A. (2001) · Food Hygiene and Safety Science (Shokuhin Eiseigaku Zasshi) · doi:10.3358/shokueishi.42.304 · Cited by 21 · see citing works
Bellé, R., Bouffant, R. L., Morales, J., Cosson, B., Cormier, P., & Mulner‐Lorillon, O. (2007) · Journal de la Société de Biologie · doi:10.1051/jbio:2007030 · Cited by 20 · see citing works
Qiu, J., Gao, H., Li, B., et al. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21691 · Cited by 17 · see citing works
Risk assessment of mixtures: possibility of prediction of interaction between chemicals
Tichý, M., Borek-Dohalský, V., Rucki, M., et al. (2002) · International Archives of Occupational and Environmental Health · doi:10.1007/s00420-002-0354-0 · Cited by 16 · see citing works
CASPASE-GLO™ 3/7 ASSAY: USE FEWER CELLS AND SPEND LESS TIME WITH THIS HOMOGENEOUS ASSAY
Moravec, R. A., & Riss, T. (2003) · Cited by 6 · see citing works
[The global status of the commercialized biotechnological/genetically modified crops: 2006].
Clive, J. (2007) · PubMed · Cited by 6 · see citing works
Song, Y., Shen, K., & He, C. (2007) · PubMed · Cited by 1 · see citing works
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Gasnier, C., Dumont, C., Benachour, N., Clair, E., Chagnon, M.-C., & Séralini, G.-E. (2009) · Toxicology · doi:10.1016/j.tox.2009.06.006 · Cited by 658 · see citing works
Self-citationEthoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity
Mesnage, R., Bernay, B., & Séralini, G.-E. (2013) · Toxicology · doi:10.1016/j.tox.2012.09.006 · Cited by 424 · see citing works
Self-citationTarazona, J. V., Court-Marques, D., Tiramani, M., Reich, H., Pfeil, R., Istace, F., & Crivellente, F. (2017) · Archives of Toxicology · doi:10.1007/s00204-017-1962-5 · Cited by 402 · see citing works
Séralini, G.-E., Clair, E., Mesnage, R., Gress, S., Defarge, N., Malatesta, M., Hennequin, D., & de Vendômois, J. S. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.08.005 · Cited by 397 · see citing works
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Mesnage, R., Defarge, N., Spiroux de Vendômois, J., & Séralini, G.-E. (2014) · BioMed Research International · doi:10.1155/2014/179691 · Cited by 342 · see citing works
Self-citationSéralini, G.-E., Clair, E., Mesnage, R., Gress, S., Defarge, N., Malatesta, M., Hennequin, D., & de Vendômois, J. S. (2014) · Environmental Sciences Europe · doi:10.1186/s12302-014-0014-5 · Cited by 299 · see citing works
Self-citationMeftaul, I. M., Venkateswarlu, K., Dharmarajan, R., Annamalai, P., Asaduzzaman, M., Parven, A., & Megharaj, M. (2020) · Environmental Pollution · doi:10.1016/j.envpol.2020.114372 · Cited by 218 · see citing works
Defarge, N., Takács, E., Lozano, V., Mesnage, R., Spiroux de Vendômois, J., Séralini, G.-E., & Székács, A. (2016) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13030264 · Cited by 205 · see citing works
Self-citationGlyphosate impairs male offspring reproductive development by disrupting gonadotropin expression
Romano, M. A., Romano, R. M., Santos, L. D., Wisniewski, P., Campos, D. A., de Souza, P. B., Viau, P., Bernardi, M. M., Nunes, M. T., & de Oliveira, C. A. (2012) · Archives of Toxicology · doi:10.1007/s00204-011-0788-9 · Cited by 196 · see citing works
Genetically modified crops safety assessments: present limits and possible improvements
Séralini, G.-E., Mesnage, R., Clair, E., Gress, S., de Vendômois, J. S., & Cellier, D. (2011) · Environmental Sciences Europe · doi:10.1186/2190-4715-23-10 · Cited by 82 · see citing works
Self-citationDown the River: Glyphosate Use in Agriculture and Birth Outcomes of Surrounding Populations
Dias, M., Rocha, R., & Soares, R. R. (2023) · Review of Economic Studies · doi:10.1093/restud/rdad011 · Cited by 50 · see citing works
Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines
Gasnier, C., Benachour, N., Clair, E., Travert, C., Langlois, F., Laurant, C., Decroix-Laporte, C., & Séralini, G.-E. (2010) · Journal of Occupational Medicine and Toxicology · doi:10.1186/1745-6673-5-29 · Cited by 49 · see citing works
Self-citationDefined plant extracts can protect human cells against combined xenobiotic effects
Gasnier, C., Laurant, C., Decroix-Laporte, C., Mesnage, R., Clair, E., Travert, C., & Séralini, G.-E. (2011) · Journal of Occupational Medicine and Toxicology · doi:10.1186/1745-6673-6-3 · Cited by 31 · see citing works
Self-citation
- Authors
- Benachour, N., & Séralini, G.-E.
- Affiliations
- University of Caen, Laboratory Estrogens and Reproduction, UPRES EA 2608, Institute of Biology, Caen 14032, France
- Venue
- Chemical Research in Toxicology
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-12-23
- Volume
- 22
- Issue
- 1
- Pages
- 97-105
- ISSN
- 0893-228X (ISSN-L)
- 1520-5010
- OpenAlex
- W2134236053
- Cited by
- 428
- References
- 52
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 15 · 2023: 19 · 2022: 30 · 2021: 26 · 2020: 33 · 2019: 31 · 2018: 28 · 2017: 31 · 2016: 27 · 2015: 23 · 2014: 32 · 2013: 21 · 2012: 31
- FWCI
- 23.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemical Research in Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Région Normandie
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Physical Sciences › Environmental Science › Pollution › Pesticide and Herbicide Environmental Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- glyphosate, herbicide adjuvants, AMPA, apoptosis, necrosis, caspase-3/7 activation, DNA fragmentation, umbilical vein endothelial cells, placental cells, embryonic kidney cells, synergistic toxicity, herbicide toxicity
- MeSH terms
- Glyphosate, Cell Line, Female, Glycine, Humans, Kidney, Necrosis, Placenta, Polyethylene Glycols, Stem Cells, Succinate Dehydrogenase, Umbilical Veins, Apoptosis, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Caspase 3, Caspase 7
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