Methylmercury chronic exposure affects the expression of DNA single-strand break repair genes, induces oxidative stress, and chromosomal abnormalities in young dyslipidemic apoe knockout mice

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dc.creatorCássia Rodrigues Roque
dc.creatorMaria Elena Crespo López
dc.creatorJacqueline Isaura Alvarez-leite
dc.creatorReinaldo Barreto Oriá
dc.creatorRonald Feitosa Pinheiro
dc.creatorLetícia Rodrigues Sampaio
dc.creatorMayumi da Nobrega Ito
dc.creatorDaniel Vieira Pinto
dc.creatorJuan De Sá Roriz Caminha
dc.creatorPaulo Iury Gomes Nunes
dc.creatorRamon da Silva Raposo
dc.creatorFlavia Almeida Santos
dc.creatorClaudia Carvalhinho Windmoeller
dc.date.accessioned2025-01-28T21:27:21Z
dc.date.accessioned2025-09-09T01:25:29Z
dc.date.available2025-01-28T21:27:21Z
dc.date.issued2021
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.tox.2021.152992
dc.identifier.issn0300-483X
dc.identifier.urihttps://hdl.handle.net/1843/79517
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofToxicology
dc.rightsAcesso Aberto
dc.subjectMetilmercúrio
dc.subjectCamundongo como animal de laboratorio
dc.subjectDNA
dc.subjectSistema nervoso central
dc.subjectCitogenética
dc.subjectIntoxicação
dc.subject.otherMethylmercury
dc.subject.otherDyslipidemia
dc.subject.otherApoE knockout mice
dc.subject.otherOxidative stress
dc.subject.otherDNA repair
dc.titleMethylmercury chronic exposure affects the expression of DNA single-strand break repair genes, induces oxidative stress, and chromosomal abnormalities in young dyslipidemic apoe knockout mice
dc.typeArtigo de periódico
local.citation.spage152992
local.citation.volume464
local.description.resumoMercury (Hg) is one of the most toxic environmental pollutants, especially when methylated, forming methylmercury (MeHg). MeHg affects DNA repair, increases oxidative stress, and predisposes to cancer. MeHg neurotoxicity is well-known, but recently MeHg-associated cardiovascular effects were recognized. This study evaluated circulating lipids, oxidative stress, and genotoxicity after MeHg-chronic exposure (20 mg/L in drinking water) in C57BL/6J wild-type and APOE knockout (ko) mice, the latter, being spontaneously dyslipidemic. Experimental mice were assigned to four groups: non-intoxicated and MeHg-intoxicated wild-type mice and non-intoxicated and MeHg-intoxicated APOE ko mice. Plasma levels of triglycerides, total cholesterol (TC), HDL, and LDL were analyzed. Liver lipid peroxidation and splenic gene expression of xeroderma pigmentosum complementation groups A, C, D, and G (XPA, XPC, XPD, and XPG), X-ray repair cross-complementing protein 1 (XRCC1), and telomerase reverse transcriptase (TERT) were measured. Fur Hg levels confirmed chronic MeHg intoxication. MeHg exposure raises TC levels both in wild-type and APOE ko mice. HDL and LDL-cholesterol levels were increased only in the MeHg-challenged APOE ko mice. MeHg increased liver lipid peroxidation, regardless of the genetic background. Unintoxicated APOE ko mice showed higher expression of TERT than all other groups. APOE deficiency increases XPA expression, regardless of MeHg intoxication. Furthermore, MeHg-intoxicated mice had more cytogenetic abnormalities, effect which was independent of APOE deficiency. More studies are needed to dissect the interactions between circulating lipids, MeHg intoxication, and DNA-repair pathways even at young age, interactions that likely play critical roles in cell senescence and the risk for chronic disorders later in life.
local.identifier.orcidhttps://orcid.org/0000-0001-8367-2061
local.identifier.orcidhttps://orcid.org/0000-0001-6601-9853
local.identifier.orcidhttps://orcid.org/0000-0002-1335-6853
local.identifier.orcidhttps://orcid.org/0000-0002-6914-5481
local.identifier.orcidhttps://orcid.org/0000-0003-3546-0974
local.identifier.orcidhttps://orcid.org/0000-0001-6385-5012
local.identifier.orcidhttps://orcid.org/0000-0002-2966-157X
local.identifier.orcidhttps://orcid.org/0000-0001-7846-7258
local.identifier.orcidhttps://orcid.org/0000-0001-8913-8636
local.identifier.orcidhttps://orcid.org/0000-0003-2996-4340
local.identifier.orcidhttps://orcid.org/0000-0003-3625-8540
local.identifier.orcidhttps://orcid.org/0000-0001-9621-1117
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0300483X21003140?via%3Dihub

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