Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells
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 t...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2567 |
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| author | Maria Inês Costa Beatriz Santos Lapa Joana Jorge Raquel Alves Isabel Marques Carreira Ana Bela Sarmento-Ribeiro Ana Cristina Gonçalves |
| author_facet | Maria Inês Costa Beatriz Santos Lapa Joana Jorge Raquel Alves Isabel Marques Carreira Ana Bela Sarmento-Ribeiro Ana Cristina Gonçalves |
| author_sort | Maria Inês Costa |
| collection | DOAJ |
| description | 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 ZnSO<sub>4</sub>) conditions and exposed to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) 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 H<sub>2</sub>O<sub>2</sub> 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. |
| first_indexed | 2024-03-09T20:37:47Z |
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| id | doaj.art-4afb72733452465bb41a504d63e42210 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:37:47Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4afb72733452465bb41a504d63e422102023-11-23T23:06:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235256710.3390/ijms23052567Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia CellsMaria Inês Costa0Beatriz Santos Lapa1Joana Jorge2Raquel Alves3Isabel Marques Carreira4Ana Bela Sarmento-Ribeiro5Ana Cristina Gonçalves6Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalLaboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalLaboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalLaboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalLaboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalLaboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, PortugalGenomic 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 ZnSO<sub>4</sub>) conditions and exposed to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) 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 H<sub>2</sub>O<sub>2</sub> 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.https://www.mdpi.com/1422-0067/23/5/2567zincDNA damageDNA repairgenomic instabilityacute myeloid leukemia |
| spellingShingle | Maria Inês Costa Beatriz Santos Lapa Joana Jorge Raquel Alves Isabel Marques Carreira Ana Bela Sarmento-Ribeiro Ana Cristina Gonçalves Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells International Journal of Molecular Sciences zinc DNA damage DNA repair genomic instability acute myeloid leukemia |
| title | Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells |
| title_full | Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells |
| title_fullStr | Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells |
| title_full_unstemmed | Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells |
| title_short | Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells |
| title_sort | zinc prevents dna damage in normal cells but shows genotoxic and cytotoxic effects in acute myeloid leukemia cells |
| topic | zinc DNA damage DNA repair genomic instability acute myeloid leukemia |
| url | https://www.mdpi.com/1422-0067/23/5/2567 |
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