Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells

Introduction: Glyphosate, an amino acid analog of glycine, is the most widely applied organophosphate pesticide worldwide and it is an active ingredient of all glyphosate-based herbicides (GBHs), including the formulation “Roundup. ” While glycine is an essential amino acid generally recognized safe...

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Main Authors: Francesca Truzzi, Daniele Mandrioli, Federica Gnudi, Paul T. J. Scheepers, Ellen K. Silbergeld, Fiorella Belpoggi, Giovanni Dinelli
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2021.643898/full
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spelling doaj-894bd5b0a05f4bc0bb57dc6ae60032612021-05-07T10:31:46ZengFrontiers Media S.A.Frontiers in Public Health2296-25652021-05-01910.3389/fpubh.2021.643898643898Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 CellsFrancesca Truzzi0Daniele Mandrioli1Daniele Mandrioli2Federica Gnudi3Paul T. J. Scheepers4Ellen K. Silbergeld5Fiorella Belpoggi6Giovanni Dinelli7Department of Agricultural Sciences, University of Bologna, Bologna, ItalyDepartment of Agricultural Sciences, University of Bologna, Bologna, ItalyCesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Bologna, ItalyCesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Bologna, ItalyRadboud Institute for Health Sciences, Radboud University Medical Center (UMC), Nijmegen, NetherlandsBloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Bologna, ItalyDepartment of Agricultural Sciences, University of Bologna, Bologna, ItalyIntroduction: Glyphosate, an amino acid analog of glycine, is the most widely applied organophosphate pesticide worldwide and it is an active ingredient of all glyphosate-based herbicides (GBHs), including the formulation “Roundup. ” While glycine is an essential amino acid generally recognized safe, both epidemiological and toxicological in vivo and in vitro studies available in literature report conflicting findings on the toxicity of GBHs. In our earlier in vivo studies in Sprague–Dawley rats we observed that exposure to GBHs at doses of glyphosate of 1.75 mg/kg bw/day, induced different toxic effects relating to sexual development, endocrine system, and the alteration of the intestinal microbiome. In the present work, we aimed to comparatively test in in vitro models the cytotoxicity of glycine and GBHs.Methods: We tested the cytotoxic effects of glycine, glyphosate, and its formulation Roundup Bioflow at different doses using MTT and Trypan Blue assays in human Caco2 and murine L929 cell lines.Results: Statistically significant dose-related cytotoxic effects were observed in MTT and Trypan Blue assays in murine (L929) and human (Caco2) cells treated with glyphosate or Roundup Bioflow. No cytotoxic effects were observed for glycine. In L929, Roundup Bioflow treatment showed a mean IC50 value that was significantly lower than glyphosate in both MTT and Trypan Blue assays. In Caco2, Roundup Bioflow treatment showed a mean IC50 value that was significantly lower than glyphosate in the MTT assays, while a comparable IC50 was observed for glyphosate and Roundup Bioflow in Trypan Blue assays. IC50 for glycine could not be estimated because of the lack of cytotoxic effects of the substance.Conclusion: Glyphosate and its formulation Roundup Bioflow, but not glycine, caused dose-related cytotoxic effects in in vitro human and murine models (Caco2 and L929). Our results showed that glycine and its analog glyphosate presented different cytotoxicity profiles. Glyphosate and Roundup Bioflow demonstrate cytotoxicity similar to other organophosphate pesticides (malathion, diazinon, and chlorpyriphos).https://www.frontiersin.org/articles/10.3389/fpubh.2021.643898/fullmechanismglyphosatecancertoxicitybiomarker
collection DOAJ
language English
format Article
sources DOAJ
author Francesca Truzzi
Daniele Mandrioli
Daniele Mandrioli
Federica Gnudi
Paul T. J. Scheepers
Ellen K. Silbergeld
Fiorella Belpoggi
Giovanni Dinelli
spellingShingle Francesca Truzzi
Daniele Mandrioli
Daniele Mandrioli
Federica Gnudi
Paul T. J. Scheepers
Ellen K. Silbergeld
Fiorella Belpoggi
Giovanni Dinelli
Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
Frontiers in Public Health
mechanism
glyphosate
cancer
toxicity
biomarker
author_facet Francesca Truzzi
Daniele Mandrioli
Daniele Mandrioli
Federica Gnudi
Paul T. J. Scheepers
Ellen K. Silbergeld
Fiorella Belpoggi
Giovanni Dinelli
author_sort Francesca Truzzi
title Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
title_short Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
title_full Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
title_fullStr Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
title_full_unstemmed Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
title_sort comparative evaluation of the cytotoxicity of glyphosate-based herbicides and glycine in l929 and caco2 cells
publisher Frontiers Media S.A.
series Frontiers in Public Health
issn 2296-2565
publishDate 2021-05-01
description Introduction: Glyphosate, an amino acid analog of glycine, is the most widely applied organophosphate pesticide worldwide and it is an active ingredient of all glyphosate-based herbicides (GBHs), including the formulation “Roundup. ” While glycine is an essential amino acid generally recognized safe, both epidemiological and toxicological in vivo and in vitro studies available in literature report conflicting findings on the toxicity of GBHs. In our earlier in vivo studies in Sprague–Dawley rats we observed that exposure to GBHs at doses of glyphosate of 1.75 mg/kg bw/day, induced different toxic effects relating to sexual development, endocrine system, and the alteration of the intestinal microbiome. In the present work, we aimed to comparatively test in in vitro models the cytotoxicity of glycine and GBHs.Methods: We tested the cytotoxic effects of glycine, glyphosate, and its formulation Roundup Bioflow at different doses using MTT and Trypan Blue assays in human Caco2 and murine L929 cell lines.Results: Statistically significant dose-related cytotoxic effects were observed in MTT and Trypan Blue assays in murine (L929) and human (Caco2) cells treated with glyphosate or Roundup Bioflow. No cytotoxic effects were observed for glycine. In L929, Roundup Bioflow treatment showed a mean IC50 value that was significantly lower than glyphosate in both MTT and Trypan Blue assays. In Caco2, Roundup Bioflow treatment showed a mean IC50 value that was significantly lower than glyphosate in the MTT assays, while a comparable IC50 was observed for glyphosate and Roundup Bioflow in Trypan Blue assays. IC50 for glycine could not be estimated because of the lack of cytotoxic effects of the substance.Conclusion: Glyphosate and its formulation Roundup Bioflow, but not glycine, caused dose-related cytotoxic effects in in vitro human and murine models (Caco2 and L929). Our results showed that glycine and its analog glyphosate presented different cytotoxicity profiles. Glyphosate and Roundup Bioflow demonstrate cytotoxicity similar to other organophosphate pesticides (malathion, diazinon, and chlorpyriphos).
topic mechanism
glyphosate
cancer
toxicity
biomarker
url https://www.frontiersin.org/articles/10.3389/fpubh.2021.643898/full
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