Oxidative damage and cytogenetic analysis in leukocytes of Parkinson’s disease patients

Background: Postmortem studies suggest excessive free radical toxicity in the substantia nigra of patients with PD. Increased lipid peroxidation and oxidative DNA damage have been reported in the CNS. Markers of oxidative stress have been identified in the blood of patients with PD. Objective: To assess the presence of spontaneous chromosome and primary or oxidative DNA damage in peripheral blood leukocytes of patients with untreated PD. Methods: Patients with de novo PD (20) and control subjects (16), matched for age, sex, and smoking habits, underwent cytogenetic analysis using the human lymphocyte micronucleus assay coupled with the fluorescence in situ hybridization technique and the Comet assay. Results: Compared with controls, patients with PD showed an increase in the incidence of spontaneous micronuclei (p < 0.001); single strand breaks (p < 0.001); and oxidized purine bases (p < 0.05). Fluorescence in situ hybridization analysis showed micronuclei harboring acentric fragments. Conclusions: There is chromosomal, primary DNA damage and oxidative DNA damage demonstrable in lymphocytes of patients with untreated PD.

[1]  Y. Itoyama,et al.  Increase in peripheral CD4 bright+ CD8 dull+ T cells in Parkinson disease. , 2001, Archives of neurology.

[2]  L. Migliore,et al.  Spontaneous and induced chromosome damage in somatic cells of sporadic and familial Alzheimer's disease patients. , 2001, Mutagenesis.

[3]  E. Melamed,et al.  Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier , 2001, Neuropharmacology.

[4]  P. Jenner Parkinson's disease, pesticides and mitochondrial dysfunction , 2001, Trends in Neurosciences.

[5]  P. Mckinnon,et al.  Linking DNA damage and neurodegeneration , 2000, Trends in Neurosciences.

[6]  M. R. Chowdhury,et al.  Recent advances in chromosome breakage syndromes and their diagnosis. , 2000, Indian pediatrics.

[7]  L. Migliore,et al.  Preferential occurrence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients , 1999, Cytogenetic and Genome Research.

[8]  A E Aust,et al.  Mechanisms of DNA oxidation. , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[9]  G. Di Chiara,et al.  Reduced dopamine in peripheral blood lymphocytes in Parkinson's disease. , 1999, Neuroreport.

[10]  G. Nappi,et al.  Determination of hydroxyl free radical formation in human platelets using high-performance liquid chromatography with electrochemical detection. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[11]  J. Morrow,et al.  Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Dobbs,et al.  Association of circulating TNF‐α and IL‐6 with ageing and parkinsonism , 1999 .

[13]  P. Morris,et al.  In Vitro and In Vivo Effects of Genistein on Murine Alveolar Macrophage TNFα Production , 1999, Inflammation.

[14]  B. Frei,et al.  Can antioxidant vitamins materially reduce oxidative damage in humans? , 1999, Free radical biology & medicine.

[15]  T. Dawson,et al.  Free Radicals as Mediators of Neuronal Injury , 1998, Cellular and Molecular Neurobiology.

[16]  W. Kuhn,et al.  Hyperhomocysteinaemia in Parkinson’s disease , 1998, Journal of Neurology.

[17]  P. Mecocci,et al.  Oxidative damage to DNA in lymphocytes from AD patients , 1998, Neurology.

[18]  C. Marsden,et al.  The causes of parkinson's disease are being unraveled and rational neuroprotective therapy is close to reality , 1998, Annals of neurology.

[19]  A. Collins,et al.  DNA damage in diabetes: correlation with a clinical marker. , 1998, Free radical biology & medicine.

[20]  B. Miller,et al.  Frontotemporal dementia: Neuropil spheroids and presynaptic terminal degeneration , 1998, Annals of neurology.

[21]  L. Migliore,et al.  Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer’s disease , 1997, Human Genetics.

[22]  Y. Shiloh,et al.  Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress? , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[23]  C D Marsden,et al.  Oxidative DNA Damage in the Parkinsonian Brain: An Apparent Selective Increase in 8‐Hydroxyguanine Levels in Substantia Nigra , 1997, Journal of neurochemistry.

[24]  Z. Katsarou,et al.  Superoxide dismutase activity in early and advanced Parkinson's disease. , 1997, Functional neurology.

[25]  J. Nygren,et al.  The comet assay: mechanisms and technical considerations. , 1996, Mutation research.

[26]  N. Hattori,et al.  Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Marsden,et al.  Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia , 1994, Annals of neurology.

[28]  C. Marín,et al.  Mitochondria1 respiratory chain activity in skeletal muscle from patients with Parkinson's disease , 1993, Neurology.

[29]  A. Collins,et al.  Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. , 1993, Carcinogenesis.

[30]  T. Lindahl Instability and decay of the primary structure of DNA , 1993, Nature.

[31]  C. Marsden,et al.  Mitochondrial function in Parkinson's disease , 1992, Annals of neurology.

[32]  M. Dizdaroglu Oxidative damage to DNA in mammalian chromatin. , 1992, Mutation research.

[33]  K. Jellinger,et al.  Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease , 1992, Neuroscience Letters.

[34]  F. Depasse,et al.  Detection of micronuclei after exposure to mitomycin C, cyclophosphamide and diethylnitrosamine by the in vivo micronucleus test in mouse splenocytes. , 1992, Mutation research.

[35]  A. Rajput,et al.  Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson's disease , 1992, Molecular and Cellular Biochemistry.

[36]  M. Green,et al.  UV-C sensitivity of unstimulated and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay: a potential diagnostic technique. , 1992, Mutation research.

[37]  A. Torroni,et al.  Mitochondrial oxidative phosphorylation defects in parkinson's disease , 1991, Annals of neurology.

[38]  D. Turnbull,et al.  Respiratory chain abnormalities in skeletal muscle from patients with Parkinson's disease , 1991, Journal of the Neurological Sciences.

[39]  P. Piccini,et al.  Platelet monoamine oxidase B activity in parkinsonian patients. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[40]  J. Parks,et al.  Abnormalities of the electron transport chain in idiopathic parkinson's disease , 1989, Annals of neurology.

[41]  A. H. V. Schapira,et al.  MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE , 1989, The Lancet.

[42]  C. Marsden,et al.  Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease , 1989, Journal of neurochemistry.

[43]  B. Ames,et al.  Normal oxidative damage to mitochondrial and nuclear DNA is extensive. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[44]  A. Yalçın,et al.  Increased erythrocyte susceptibility to lipid peroxidation in human Parkinson's disease , 1988, Neuroscience Letters.

[45]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[46]  A. Członkowska,et al.  [3H]Spiperone binding to lymphocyte in extrapyramidal disease and in aging , 1987, Brain, Behavior, and Immunity.

[47]  Voon Wee Yong,et al.  Idiopathic Parkinson's disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients , 1986, Neuroscience Letters.

[48]  P. Cerutti Prooxidant states and tumor promotion. , 1985, Science.

[49]  D. Graham Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. , 1978, Molecular pharmacology.

[50]  D. Graham,et al.  Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. , 1978, Molecular pharmacology.

[51]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[52]  Hitoshi Takahashi,et al.  Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses , 2004, Acta Neuropathologica.

[53]  M. Parrinello,et al.  Mechanism of DNA oxidation , 2004 .

[54]  R. Waring,et al.  A Review of Xenobiotic Metabolism Enzymes in Parkinson's Disease and Motor Neuron Disease , 2001, Drug metabolism and drug interactions.

[55]  P. Mcgeer,et al.  Mechanisms of cell death in Alzheimer disease--immunopathology. , 1998, Journal of neural transmission. Supplementum.

[56]  S. Loft,et al.  Cancer risk and oxidative DNA damage in man , 1997, Journal of Molecular Medicine.

[57]  H. Gerster Intermediate cancer biomarkers and their use in beta-carotene studies in humans. , 1996, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[58]  M. Yahr,et al.  Impaired oxidative decarboxylation of pyruvate in fibroblasts from patients with Parkinson's disease , 1994, Journal of neural transmission. Parkinson's disease and dementia section.

[59]  E. Tolosa,et al.  Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease. , 1993, Neurology.

[60]  M. Fenech,et al.  The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. , 1993, Mutation research.

[61]  E. Stadtman,et al.  Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. , 1993, Annual review of biochemistry.

[62]  C. Marsden,et al.  Platelet mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson Disease Research Group. , 1992, Annals of neurology.

[63]  H. Yoshino,et al.  Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson's disease , 1992, Journal of neural transmission. Parkinson's disease and dementia section.

[64]  A. Schapira,et al.  Mitochondrial DNA analysis in Parkinson's disease , 1990, Movement disorders : official journal of the Movement Disorder Society.

[65]  R. Dean,et al.  Free radicals, lipids and protein degradation , 1986 .