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Updated: Oct 11, 2025
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and
Robin Mesnage1, Mariam Ibragim1, Daniele Mandrioli2
1Gene Expression and Therapy Group, Department of Medical and Molecular Genetics, Faculty of Life Sciences & Medicine, Guy's Hospital, King's College London, London SE1 9RT, UK.
Abstract:
Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate.
Insights
Glyphosate-based herbicides (GBHs) like Roundup activate cellular pathways linked to cancer more than glyphosate alone. Studies show GBHs induce oxidative stress and liver damage, suggesting higher carcinogenic risk.
Area of Science:
- Toxicology and Carcinogenesis
- Environmental Health
- Molecular Biology
Background:
- The carcinogenic potential of glyphosate-based herbicides (GBHs) compared to glyphosate alone is debated.
- GBHs exhibit higher cytotoxicity than glyphosate, suggesting a potentially greater capacity for activating carcinogenic pathways.
- Understanding these differences is crucial for public health and regulatory assessment.
Purpose of the Study:
- To compare the in vitro and in vivo effects of glyphosate with representative GBHs (Roundup formulations).
- To investigate whether GBHs activate cellular mechanisms driving carcinogenesis more potently than glyphosate.
- To assess molecular and histological changes associated with GBH exposure.
Main Methods:
- In vitro: Mammalian stem cell-based ToxTracker system comparing glyphosate with MON 52276, MON 76473, and MON 76207.
- In vivo: Molecular profiling of liver and kidney in Sprague-Dawley rats exposed to glyphosate or MON 52276 for 90 days.
- Analyses included histology, gene expression, small RNA profiling, DNA methylation, and DNA damage assessment.
Main Results:
- In vitro, MON 52276 and MON 76473 activated oxidative stress and unfolded protein responses, unlike glyphosate.
- In vivo, MON 52276 induced hepatic steatosis and necrosis, altered gene expression related to DNA damage (TP53) and circadian rhythms, and affected small RNA profiles.
- Both glyphosate and MON 52276 altered liver gene expression; MON 52276 caused more significant histological changes, and glyphosate increased DNA damage.
Conclusions:
- Roundup formulations induce more biological changes linked to carcinogenesis than glyphosate alone.
- GBHs demonstrate a greater potential to activate cellular stress responses and cause tissue damage.
- Findings highlight the importance of evaluating GBHs as complex mixtures rather than solely glyphosate.
