Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells

Abstract

Abstract. Roundup

Re-registration Challenges of Glyphosate in the European Union

“…Three glyphosate-based formulations, Roundup Express R , Roundup Bioforce R , Roundup GT R and Roundup GT Plus R at 5% dilutions corresponding to 0.04-2.3 mg/ml concentrations of glyphosate showed 22-97% inhibition of the mitochondial activity and activation of caspase 3/7 enzymes of HepG2 cells, while such levels of inhibition with glyphosate alone could be achieved only at or above 20 mg/ml concentration (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013a). Effects were similar, but even somewhat stronger on the more sensitive human Hep3G hepatic cell line (Gasnier et al, 2010).…”

“…Although reviews of genotoxicity studies deemed DNA damage by glyphosate and glyphosate-based formulations secondary to cytotoxic effects (Kier and Kirkland, 2013;Kier, 2015), DNA-damaging effects and genotoxicity of glyphosate and particularly of its formulations (Roundup R , Glyfos R , Glyphogan R , Glyphosate-Biocarb R , etc.) on vertebrates (murine and human cells) (Bolognesi et al, 1997;Koller et al, 2012;Young et al, 2015;Townsend et al, 2017), cytotoxic effects of glyphosate-based herbicides on human embryonic and placental cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009Gasnier et al, , 2010Mesnage et al, 2013a,b), indication of endocrine disrupting effects by showing activity on estrogen receptors in human hormone-dependent breast cancer cells (Thongprakaisang et al, 2013;Mesnage et al, 2017a), inhibition of the biosynthesis of testosterone and estradiol (Romano et al, 2010) and progesterone (Young et al, 2015) or inhibitory effects on aromatase, a key enzyme in steroid hormone biosynthesis (Cassault-Meyer et al, 2014;Defarge et al, 2016), teratogenic effects on vertebrates by inhibiting the retinoic acid signaling pathway (Lajmanovich et al, 2003;Paganelli et al, 2010;Carrasco, 2013), birth defects in rats , and nephrotoxic and hepatotoxic effects of Roundup R have been demonstrated in rats in connection to RR GM maize (originally published in the journal Food and Chemical Toxicology in September 2012, but retracted by the journal in November 2013 following an alleged intervention from the industry stakeholder (Foucart, 2016), and subsequently republished in another journal a year later) . The analysis of kidney and liver tissues from the same rats by molecular profiling (transcriptomics, proteomics, metabolomics) confirmed pathology of these organs in the lowest dose Roundup R treatment group culminating in non-alcoholic fatty liver disease (Mesnage et al, 2015a(Mesnage et al, ,b, 2017a.…”

“…In general, the most sensitive cell lines appeared to be the human hematopoietic Epstein-Barr virus transformed lymphocyte Raji cells (Townsend et al, 2017), regenerative fin cell lines of fish origin , human epithelial HaCaT keratinocyte cells (ElieCaille et al, 2010;Heu et al, 2012a,b;Qin et al, 2017) and a murine neuroectodermal stem cell-like line, NE-4C . In contrast, cell types with the lowest apparent sensitivity were human choriocarcinoma cells (JEG3) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Romano et al, 2010;Mesnage et al, 2013a), human chorioplacental cells (JAr) (Young et al, 2015), human hepatoma cells (HepG2) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009Gasnier et al, , 2010, murine osteoblast precursor cells (MC3T3-E1) (Farkas et al, 2018), human embryonic kidney cells (HEK293) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013a), and human primary neonate umbilical vein endothelial cells (HUVEC) (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009). Cytotoxicity has also been detected by other biochemical markers e.g., mitochondrial functions, release of lactate dehydrogenase, cell proliferation determined by the use of sulforhodamine B, or membrane integrity and lysosomal activities indicated by the uptake of neutral red dye (Koller et al, 2012;Defarge et al, 2016).…”

“…Roundup Transorb R exerted cytotoxicity on a zebrafish (Danio rerio) hepatocyte cell line ZF-L at concentrations as low as 0.068-0.27 µg/ml (corresponding to glyphosate concentrations of 0.033-0.13 µg/ml), due mostly to lysosomal instability and inhibition of mitochondrial function, and slightly to impaired cell membrane integrity. Synergistic detrimental effects were observed when Roundup Transorb R was applied with an insecticide formulation (Furadan 350 FIGURE 3 | In vitro cytotoxicity of glyphosate (light columns) and its formulated preparation Roundup ® (dark columns) on various cell lines Raji: human hematopoietic Raji (Epstein-Barr virus transformed human lymphocyte) cells (Townsend et al, 2017), DIMF, diploid fin cell line from the Oriental weather loach Misgurnus anguillicaudatus ; HaCaT, human epithelial keratinocyte cells (Elie-Caille et al, 2010); NE-4C, murine stem cell-like neuroectodermal cells ; Hep-2, human epithelial type 2 (HeLa contaminant) cells (Mañas et al, 2009); GM38, human fibroblast cells (Monroy et al, 2005); HT1080, human fibrosarcoma cells (Monroy et al, 2005); HUVEC, primary neonate human umbilical vein endothelial cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009); HEK293, embryonic kidney cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013a); MC3T3-E1, murine osteoblast precursor cells (Farkas et al, 2018); HepG2, human hepatoma cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009); JAr, human chorioplacental cells (Young et al, 2015); JEG3, human choriocarcinoma cells (Benachour et al, 2007;Benachour and Séralini, 2009;Gasnier et al, 2009;Mesnage et al, 2013aMesnage et al, , 2017a. Plain and grid column patterns indicate cytotoxicity detected by MTT test and mutagenicity tests, respectively.…”

Glyphosate-based phospho-organic herbicides – an outline of action, metabolism and the selected effects on humans and other organisms

“…decre asedactivity of microsomal aromatase at a concentration of 0.5% of both chemical factors in all experimental systems [56] humanHepG2 and MDA-MB453-kb2 line cells(GP+POEA)…”