Abstract
Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA(4977) deletion were quantitated in samples with- (n = 11) and without-DS (n = 31). Samples with-DS showed 30% lower mtDNA (DS(MT-ND1/18Sratio): 1.48 ± 0.72 versus non-DS(MT-ND1/18Sratio): 2.10 ± 1.59; p = 0.647) and 30% higher frequency of the mtDNA(4977) deletion (DS(% frequency mtDNA(4977)) deletion: 0.0086 ± 0.0166 versus non-DS(% frequency mtDNA(4977)) deletion: 0.0066 ± 0.0124, p = 0.514) than samples without-DS. The BACH1 and microRNA-155 (miR-155) genes are located in chromosome 21, and their products have demonstrated roles during oxidative stress. BACH1 and miR-155 expression did not differ in hearts with- and without-DS. An association between BACH1 and miR-155 expression was detected in hearts without-DS, suggesting alterations between BACH1-miR-155 interactions in the DS settings.
Keywords:
Anthracycline-related cardiotoxicity; Down syndrome; mitochondrial DNA; oxidative stress.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adolescent
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Adult
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Aged
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Anthracyclines / adverse effects*
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Anthracyclines / therapeutic use
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Antibiotics, Antineoplastic / adverse effects*
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Antibiotics, Antineoplastic / therapeutic use
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Base Sequence
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Basic-Leucine Zipper Transcription Factors / biosynthesis
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Basic-Leucine Zipper Transcription Factors / genetics*
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Cardiotoxicity
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Child
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Child, Preschool
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Chromosomes, Human, Pair 21
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DNA, Mitochondrial / genetics*
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Down Syndrome / genetics*
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Fanconi Anemia Complementation Group Proteins / biosynthesis
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Fanconi Anemia Complementation Group Proteins / genetics*
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Female
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Genes, Mitochondrial
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Heart Diseases / chemically induced
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Heart Diseases / genetics
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Heart Diseases / pathology
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Humans
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Infant
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Leukemia, Myeloid, Acute / drug therapy
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Male
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MicroRNAs / biosynthesis
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MicroRNAs / genetics*
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Middle Aged
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Mitochondria / drug effects
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Myocardium / metabolism
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Oxidative Stress / genetics
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Oxidative Stress / physiology
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Pilot Projects
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RNA, Messenger / genetics
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Sequence Analysis, DNA
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Sequence Deletion / genetics
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Young Adult
Substances
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Anthracyclines
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Antibiotics, Antineoplastic
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BACH1 protein, human
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Basic-Leucine Zipper Transcription Factors
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DNA, Mitochondrial
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Fanconi Anemia Complementation Group Proteins
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MIRN155 microRNA, human
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MicroRNAs
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RNA, Messenger