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Volume 23
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10.3390/ijms23052567
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Article

Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells

by
Maria Inês Costa
1,2,
Beatriz Santos Lapa
1,2,
Joana Jorge
1,2,3,4,
Raquel Alves
1,2,3,4,
Isabel Marques Carreira
2,3,4,5,
Ana Bela Sarmento-Ribeiro
1,2,3,6 and
Ana Cristina Gonçalves
1,2,3,4,*
1
Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal
2
Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal
3
Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal
4
Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal
5
Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3004-531 Coimbra, Portugal
6
Hematology Service, Centro Hospitalar e Universitário de Coimbra (CHUC), 3000-061 Coimbra, Portugal
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(5), 2567; https://doi.org/10.3390/ijms23052567
Submission received: 27 January 2022 / Revised: 20 February 2022 / Accepted: 23 February 2022 / Published: 25 February 2022
(This article belongs to the Special Issue DNA Damage Response (DDR) and DNA Repair)
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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.
Keywords: zinc; DNA damage; DNA repair; genomic instability; acute myeloid leukemia zinc; DNA damage; DNA repair; genomic instability; acute myeloid leukemia

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MDPI and ACS Style

Costa, M.I.; Lapa, B.S.; Jorge, J.; Alves, R.; Carreira, I.M.; Sarmento-Ribeiro, A.B.; Gonçalves, A.C. Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells. Int. J. Mol. Sci. 2022, 23, 2567. https://doi.org/10.3390/ijms23052567

AMA Style

Costa MI, Lapa BS, Jorge J, Alves R, Carreira IM, Sarmento-Ribeiro AB, Gonçalves AC. Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells. International Journal of Molecular Sciences. 2022; 23(5):2567. https://doi.org/10.3390/ijms23052567

Chicago/Turabian Style

Costa, Maria Inês, Beatriz Santos Lapa, Joana Jorge, Raquel Alves, Isabel Marques Carreira, Ana Bela Sarmento-Ribeiro, and Ana Cristina Gonçalves. 2022. "Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells" International Journal of Molecular Sciences 23, no. 5: 2567. https://doi.org/10.3390/ijms23052567

APA Style

Costa, M. I., Lapa, B. S., Jorge, J., Alves, R., Carreira, I. M., Sarmento-Ribeiro, A. B., & Gonçalves, A. C. (2022). Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells. International Journal of Molecular Sciences, 23(5), 2567. https://doi.org/10.3390/ijms23052567

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