Abstract

Exposure to environmental endocrine disruptors has been associated with an increased frequency of thyroid pathology. In this study, we evaluated the effects of various concentrations of methylmercury (MeHg) on immortalized, non-tumorigenic thyroid cells (Nthy-ori-3-1). Exposure to MeHg at 2.5 and 5 µM for 24 h caused a reduction in cell viability with a decrease of the cell population in sub-G0 phase, as detected by MTT and flow cytometry. Conversely, MeHg at the lower concentration of 0.1 µM increased the cell viability with a rise of G2/M phase. An immunoblot analysis showed higher expression levels of phospho-ERK and not of phospho-Akt. Further enhancement of the cell growth rate was observed after a prolonged exposure of the cells up to 18 days to MeHg 0.1 µM. The present findings demonstrate the toxicity of high concentrations of MeHg on thyroid cells, while showing that treatment with lower doses of Hg, as may occur after prolonged exposure to this environmental contaminant, exerts a promoting effect on thyroid cell proliferation, by acting on the ERK-mediated pro-oncogenic signal transduction pathway.

Highlights

  • In the last few years, thyroid cancer incidence has increased significantly [1]

  • We analyzed the effects of methylmercury (MeHg) on immortalized, non-tumorigenic ‘normal’ thyroid cells Nthy-ori-3-1 and the molecular changes occurring after exposure Itnot

  • 24 h of trecaeltlmvCioeanbnvitlei,tryscey(laytb,ooMflueutH2og0r%aimtvtshe.eturcnoitcnrceaeanntetardaltycieoslnilsso)fs(F0hi.1gouμwrMee1dd)e. ttNehremextip,nwerdeesaeevsnaiglcuneiaftioceadfntathienricesrfeefeacsietnsooGffNM2t/heMyH-ogproih-n3a-c1seell of the cell cycle at a added at hcGyoi2gcn/lMheccGcyeeep2lcplrn/rlMhveotciagrpaopsarrbeenhotislagiocisostrfeiyeeontns(onhsatofi.ebortAfonachue0f.etttlAi.elco12refc0tnly2μe%l s4crcMlyv2eh(4cs5,.aloehutafμnaoantMttrfrdceateoar)acenattoma(ecnntFdemecniinecgnetentrnu,lctaltrcsrt,ra)yieceto(tyiaFnoot2sinofgol)efuu.olfuorof0eor0f.ri11.mi1c)mμ.eμeNMeltMtlreri,xip,ccata,oananwnnpddaaeualaleyynnlvssaaiiiitssnnliucscsorahrhenteooeaawdwsiseneetedhodoseftfuhtcehcefebfeelelp-lclpGprtepros0seopoespufnpeulMcnahelctaeaieooHtsfinoogeafnionrawinisnsrehcuisesbienlu-lnbin-MeHg was

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Summary

Introduction

In the last few years, thyroid cancer incidence has increased significantly [1]. The presence of tumors of all sizes excludes that this increment is due only to more intensive and sensitive diagnostic procedures and suggests the involvement, as additional causative factors, of environment or lifestyle changes [2]. High levels of Hg, recently detected together with other heavy metals in volcanic areas [7,8], have been suspected to play a co-causative role in the high incidence of thyroid cancer, as earlier proposed by Zaichick et al [9] to date, the molecular alterations occurring in thyroid cells exposed to environmental heavy metals, able to promote the transformation and/or the selective growth of neoplastic cells, are not known, as well as the doses and duration of exposure necessary for such an action [10]. We analyzed the effects of methylmercury (MeHg) on immortalized, non-tumorigenic ‘normal’ thyroid cells Nthy-ori-3-1 and the molecular changes occurring after exposure Itnot.

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