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Title: Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells
Authors: Costa, Maria Inês 
Lapa, Beatriz Santos 
Jorge, Joana 
Alves, Raquel 
Carreira, Isabel Marques 
Sarmento-Ribeiro, Ana Bela 
Gonçalves, Ana Cristina 
Keywords: zinc; DNA damage; DNA repair; genomic instability; acute myeloid leukemia
Issue Date: 25-Feb-2022
Project: UID/NEU/04539/2019 
FCT - grant SFRH/BD/145531/2019 
FCT - grant 2020.08261.BD 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 23
Issue: 5
Abstract: Genomic instability is prevented by the DNA damage response (DDR). Micronutrients, like zinc (Zn), are cofactors of DDR proteins, and micronutrient deficiencies have been related to increased cancer risk. Acute myeloid leukemia (AML) patients commonly present Zn deficiency. Moreover, reports point to DDR defects in AML. We studied the effects of Zn in DDR modulation in AML. Cell lines of AML (HEL) and normal human lymphocytes (IMC) were cultured in standard culture, Zn depletion, and supplementation (40 μM ZnSO4) conditions and exposed to hydrogen peroxide (H2O2) or ultraviolet (UV) radiation. Chromosomal damage, cell death, and nuclear division indexes (NDI) were assessed through cytokinesis-block micronucleus assay. The phosphorylated histone H2AX (yH2AX) expression was monitored at 0 h, 1 h, and 24 h after exposure. Expression of DDR genes was evaluated by quantitative real time polymerase chain reaction (qPCR). Zn supplementation increased the genotoxicity of H2O2 and UV radiation in AML cells, induced cytotoxic and antiproliferative effects, and led to persistent yH2AX activation. In contrast, in normal lymphocytes, supplementation decreased damage rates, while Zn depletion favored damage accumulation and impaired repair kinetics. Gene expression was not affected by Zn depletion or supplementation. Zn presented a dual role in the modulation of genome damage, preventing damage accumulation in normal cells and increasing genotoxicity and cytotoxicity in AML cells.
ISSN: 1422-0067
DOI: 10.3390/ijms23052567
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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