In-depth comparative toxicogenomics of glyphosate and Roundup herbicides: Histopathology, transcriptome and epigenome signatures, and DNA damage

Whether or not glyphosate activates cellular mechanisms involved in carcinogenesis remains controversial. We tested whether glyphosate and three glyphosate-based commercial herbicide formulations activate mechanisms known to be key characteristics of carcinogens. The mammalian stem cell-based genotoxicity ToxTracker assay showed that the representative EU formulation Roundup MON 52276 and the UK formulation Roundup MON 76473, but not glyphosate and the US Roundup formulation MON 76207, activated oxidative stress and unfolded protein responses. High-throughput molecular profiling of liver function was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (both at 0.5, 50, 175 mg/kg bw/day glyphosate equivalent concentration) for 90 days. Histopathology and serum biochemistry analysis showed that MON 52276 but not glyphosate treatment increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation ...