Alternation between toxic and proliferative effects of Roundup® on human thyroid cells at different concentrations.

Autor:	Dal' Bó IF; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil., Teixeira ES; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil., Rabi LT; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil., Peres KC; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil., Nascimento M; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil., Chiamolera MI; São Leopoldo Mandic School of Medicine, Campinas, Brazil., Máximo V; Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.; Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal.; Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal., Bufalo NE; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil.; Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal., Ward LS; Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas, Campinas, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 Jul 29; Vol. 13, pp. 904437. Date of Electronic Publication: 2022 Jul 29 (Print Publication: 2022).
DOI:	10.3389/fendo.2022.904437
Abstrakt:	Endocrine-disrupting and carcinogenic effects of glyphosate have long been suspected, but little is known about the effect of compounds used in real life at different concentrations, neither in normal nor in thyroid tumor cells. As cancer cells may have different sensitivities and the effect of the product containing glyphosate may be different from that produced by the active ingredient alone, including the Acceptable Occupational Exposure Level (AOEL=160µg/L) and the Acceptable Daily Intake (ADI=830µg/L) determined by ANVISA, we used two human thyroid-derived cell lines, Nthy-ori 3-1 (from normal follicular cells) and TPC-1 (from papillary carcinoma), to test 15 different concentrations of Roundup® Original DI. Trypan blue (TB), CCK-8 and BrdU assays were used to evaluate cytotoxicity, metabolic activity and proliferation with 24h and 48h exposures in technical and biological triplicates. TB showed an important toxic effect, especially after 24h of exposure, in both cell lines. The AOEL concentration caused the death of 43% and 50% of the Nthy-ori and TPC-1 cells, respectively, in 24 h, while ADI resulted in 35% and 58% of cell death. After 48h of exposure, AOEL and ADI caused a lower number of dead Nthy-ori (33% and 18%) and TPC-1 (33% and 37%) cells, respectively, suggesting that the toxic effect of the product disappears and/or both strains have repair mechanisms that protect them from longer exposures. On the other hand, the CCK-8 assay showed that small concentrations of Roundup have a proliferative effect: 6.5µg/L increased the number of both Nthy-ori and TPC-1 cells at 24h, and the BrdU assay confirmed the stimulatory effect with a 321% increase in the absorbance of Nthy-ori cells at 48h. The herbicide produced even more frequent increases in the BrdU absorbance of TPC-1 cells, mainly at 24h. We conclude that thyroid cells exposed to Roundup present a nonmonotonic dual dose-response curve. Low concentrations of the pesticide, considered acceptable, cause significant cell death but also have an important proliferative effect, especially on TPC-1 cells. This herbicide, widely used around the world, may play a role in the increased incidence rate of thyroid nodules and cancer that has been observed in recent decades. Competing Interests: LSW is a Category 1 Research Fellow at the National Council for Scientific and Technological Development (CNPq). The remaining authors declare that the research was carried out in the absence of any commercial or financial relationship that could be interpreted as a potential conflict of interest. (Copyright © 2022 Dal’ Bó, Teixeira, Rabi, Peres, Nascimento, Chiamolera, Máximo, Bufalo and Ward.)
Databáze:	MEDLINE
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