Hepatoma tissue culture (HTC) cells as a model for investigating the effects of low concentrations of herbicide on cell structure and function
Abstract
Previous studies on mice fed genetically modified (GM) soybean demonstrated modifications of the mitochondrial functions and of the transcription/splicing pathways in hepatocytes. The cause(s) of these alterations could not be conclusively established but, since the GM soybean used is tolerant to glyphosate and was treated with the glyphosate-containing herbicide Roundup , the possibility exists that the effects observed may be due to herbicide residues. In order to verify this hypothesis, we treated HTC cells with 1-10mM Roundup and analysed cellular features by flow cytometry, fluorescence and electron microscopy. Under these experimental conditions, the death rate and the general morphology of HTC cells were not affected, as well as most of the cytoplasmic organelles. However, in HTC-treated cells, lysosome density increased and mitochondrial membranes modified indicating a decline in the respiratory activity. Moreover, nuclei underwent morpho-functional modifications suggestive of a decreased transcriptional/splicing activity. Although we cannot exclude that other factors than the presence of the herbicide residues could be responsible for the cellular modifications described in GM-fed mice, the concordance of the effects induced by low concentrations of Roundup on HTC cells suggests that the presence of Roundup residues could be one of the factors interfering with multiple metabolic pathways.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This toxic effect was reproduced by the application of R herbicide directly to hepatocytes in culture.
“Furthermore, this toxic effect was reproduced by the application of R herbicide directly to hepatocytes in culture [15].”
From Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize (2014) · cites this paper as [15]
Cites
Reers, M., Smith, T. W., & Chen, L. B. (1991) · Biochemistry · doi:10.1021/bi00232a015 · Cited by 1,052 · see citing works
A new staining procedure for electron microscopical cytology
Bernhard, W. (1969) · Journal of Ultrastructure Research · doi:10.1016/s0022-5320(69)80016-x · Cited by 819 · 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
Development, Identification, and Characterization of a Glyphosate‐Tolerant Soybean Line
Padgette, S. R., Kolacz, K. H., Delannay, X., Re, D. B., LaVallee, B. J., Tinius, C. N., Rhodes, W. K., Otero, Y. I., Barry, G. F., Eichholtz, D. A., et al. (1995) · Crop Science · doi:10.2135/cropsci1995.0011183x003500050032x · Cited by 610 · see citing works
Shaw, P., & Jordan, E. G. (1995) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cb.11.110195.000521 · Cited by 372 · see citing works
Walsh, L. P., McCormick, C., Martin, C. F., & Stocco, D. (2000) · Environmental Health Perspectives · doi:10.1289/ehp.00108769 · Cited by 339 · 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
Jiraungkoorskul, W., Upatham, E. S., Kruatrachue, M., et al. (2003) · Environmental Toxicology · doi:10.1002/tox.10123 · Cited by 216 · see citing works
Potential Risks and Benefits of Phytoestrogen-Rich Diets
Cassidy (2003) · International Journal for Vitamin and Nutrition Research · doi:10.1024/0300-9831.73.2.120 · Cited by 187 · see citing works
Monitoring glyphosate residues in transgenic glyphosate‐resistant soybean
Arregui, M., Lenardón, A., Sanchez, D., et al. (2003) · Pest Management Science · doi:10.1002/ps.775 · Cited by 181 · see citing works
Sanvido, O., Romeis, J., & Bigler, F. (2007) · Springer eBooks · doi:10.1007/10_2007_048 · Cited by 163 · see citing works
Glyphosate‐based pesticides affect cell cycle regulation
Marc, J., Mulner‐Lorillon, O., & Bellé, R. (2004) · Biology of the Cell · doi:10.1016/j.biolcel.2003.11.010 · Cited by 153 · 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
Schwarzacher, H. G., & Wachtler, F. J. (1993) · Anatomy and Embryology · doi:10.1007/bf00187008 · Cited by 123 · see citing works
Environmental Risks of Pesticides Versus Genetic Engineering for Agricultural Pest Control
Paoletti, M. G., & Pimentel, D. (2000) · Journal of Agricultural and Environmental Ethics · doi:10.1023/a:1009571131089 · Cited by 117 · see citing works
Malatesta, M., Caporaloni, C., Gavaudan, S., Rocchi, M. B. L., Serafini, S., Tiberi, C., & Gazzanelli, G. (2002) · Cell Structure and Function · doi:10.1247/csf.27.173 · Cited by 112 · see citing works
Self-citationJordan, E. G., & Mcgovern, J. H. (1981) · Journal of Cell Science · doi:10.1242/jcs.52.1.373 · Cited by 110 · see citing works
Ultrastructural analysis of testes from mice fed on genetically modified soybean
Vecchio, L., Cisterna, B., Malatesta, M., Martin, T., & Biggiogera, M. (2009) · European Journal of Histochemistry · doi:10.4081/920 · Cited by 95 · see citing works
Self-citationSzarek, J., Siwicki, A. K., Andrzejewska, A., et al. (2000) · Marine Environmental Research · doi:10.1016/s0141-1136(00)00088-x · Cited by 91 · see citing works
A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing
Malatesta, M., Boraldi, F., Annovi, G., Baldelli, B., Battistelli, S., Biggiogera, M., & Quaglino, D. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0476-x · Cited by 88 · see citing works
Self-citationMalatesta, M., Biggiogera, M., Manuali, E., & Rocchi, M. (2009) · European Journal of Histochemistry · doi:10.4081/851 · Cited by 77 · see citing works
Self-citationEl-Demerdash, F. M., Yousef, M. I., & El‐Agamy, E. I. (2001) · Journal of Environmental Science and Health Part B · doi:10.1081/pfc-100000914 · Cited by 76 · see citing works
Lappé, M., Bailey, E., Childress, C., et al. (1998) · Journal of Medicinal Food · doi:10.1089/jmf.1998.1.241 · Cited by 71 · see citing works
Hietanen, E. K., Linnainmaa, K., & Vainio, H. (1983) · Acta Pharmacologica et Toxicologica · doi:10.1111/j.1600-0773.1983.tb01876.x · Cited by 69 · 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
Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean
Malatesta, M., Caporaloni, C., Rossi, L., Battistelli, S., Rocchi, M. B. L., Tonucci, F., & Gazzanelli, G. (2002) · Journal of Anatomy · doi:10.1046/j.0021-8782.2002.00103.x · Cited by 68 · see citing works
Self-citationUltrastructural cytochemical analyses of nuclear functional architecture.
Fakan, S. (2004) · PubMed · doi:10.4081/854 · Cited by 67 · see citing works
Mamy, L., Gabrielle, B., & Barriuso, E. (2008) · Pest Management Science · doi:10.1002/ps.1519 · Cited by 48 · see citing works
A new approach to map transcription sites at the ultrastructural level.
Testillano, P. S., Gorab, E., & Risueño, M. C. (1994) · Journal of Histochemistry & Cytochemistry · doi:10.1177/42.1.7505298 · Cited by 47 · see citing works
Reversibility of hepatocyte nuclear modifications in mice fed on genetically modified soybean.
Malatesta, M., Tiberi, C., Baldelli, B., Battistelli, S., Manuali, E., & Biggiogera, M. (2005) · PubMed · doi:10.4081/950 · Cited by 45 · see citing works
Self-citationRelationship between chromatin and perichromatin granules in cadmium-treated isolated hepatocytes
Puvion-dutilleul, F., & Puvion, E. (1981) · Journal of Ultrastructure Research · doi:10.1016/s0022-5320(81)80125-6 · Cited by 40 · see citing works
Kuiper, H. A., König, A., Kleter, G. A., et al. (2004) · Food and Chemical Toxicology · doi:10.1016/j.fct.2004.02.004 · Cited by 37 · see citing works
Ultrastructural and morphometrical analyses of the brown adipocyte nucleus in a hibernating dormouse
Zancanaro, C., Malatesta, M., Vogel, P., et al. (1993) · Biology of the Cell · doi:10.1016/0248-4900(93)90263-e · Cited by 31 · see citing works
Self-citationLafarga, M., Berciano, M. T., & Andrés, M. A. (1993) · Anatomy and Embryology · doi:10.1007/bf00185894 · Cited by 24 · see citing works
Effects of phytoestrogens on the trophoblast tumour cell lines BeWo and Jeg3.
Plessow, D., Waldschläger, J., Richter, D. U., et al. (2003) · PubMed · Cited by 23 · see citing works
Neel, J. V. (1998) · Environmental and Molecular Mutagenesis · doi:10.1002/(sici)1098-2280(1998)31:1 · Cited by 19 · see citing works
Ovidi, E., Gambellini, G., Taddei, A. R., et al. (2001) · Toxicology in Vitro · doi:10.1016/s0887-2333(00)00064-3 · Cited by 17 · see citing works
A new sensitive cell culture test for the assessment of pesticide toxicity
Bertheussen, K., Yousef, M. I., & Figenschau, Y. (1997) · Journal of Environmental Science and Health Part B · doi:10.1080/03601239709373082 · Cited by 17 · see citing works
Boerrigter, M. E. T. I., & Vijg, J. (1997) · Environmental and Molecular Mutagenesis · doi:10.1002/(sici)1098-2280(1997)29:3 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines
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
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
Self-citationRetractedSéralini, 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-citationA literature review on the safety assessment of genetically modified plants
Domingo, J. L., & Giné Bordonaba, J. (2011) · Environment International · doi:10.1016/j.envint.2011.01.003 · Cited by 272 · see citing works
Schütte, G., Eckerstorfer, M., Rastelli, V., Reichenbecher, W., Restrepo-Vassalli, S., Ruohonen-Lehto, M., Saucy, A.-G. W., & Mertens, M. (2017) · Environmental Sciences Europe · doi:10.1186/s12302-016-0100-y · Cited by 249 · see citing works
Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids
Forsythe, S. D., Devarasetty, M., Shupe, T., Bishop, C., Atala, A., Soker, S., & Skardal, A. (2018) · Frontiers in Public Health · doi:10.3389/fpubh.2018.00103 · Cited by 112 · 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
- Authors
- Malatesta, M., Perdoni, F., Santin, G., Battistelli, S., Muller, S., & Biggiogera, M.
- Affiliations
- University of Verona (IT)
- University of Pavia (IT)
- University of Urbino (IT)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Malatesta, M.
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 22
- Issue
- 8
- Pages
- 1853-1860
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W2152603056
- Cited by
- 50
- References
- 39
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2021: 5 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Genetically Modified Organisms Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- Roundup, glyphosate, herbicide residues, transgenic soybean, hepatocyte cytotoxicity
- MeSH terms
- Glyphosate, Animals, Dose-Response Relationship, Drug, Flow Cytometry, Fluorescence, Glycine, Carcinoma, Hepatocellular, Herbicides, Liver Neoplasms, Lysosomes, Microscopy, Electron, Models, Biological, Pesticide Residues, Transcription, Genetic, Tumor Cells, Cultured, Cell Death, Mitochondrial Membranes, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review