Zeitschrift für Orthomolekulare Medizin 2018; 16(01): 18-23
DOI: 10.1055/a-0575-2997
© Georg Thieme Verlag KG Stuttgart · New York

Oxidativer Stress und epigenetische Effekte – genetische Ursachen und deren Folgen

Eckart Schnakenberg
Further Information

Publication History

Publication Date:
23 April 2018 (online)


Die Aktivität von Phase-I-Enzymen, die an der Entstehung von oxidativem Stress beteiligt sind, und kompensatorisch wirkenden Phase-II-Enzymen ist genetisch determiniert. Träger ungünstiger Genvarianten haben höheren oxidativen Stress und ein erhöhtes Risiko für chronisch-entzündliche oder neurodegenerative Erkrankungen. Oxidativer Stress und epigenetische Modifikationen wie die DNA-Methylierung beeinflussen neben anderen Faktoren die Genexpression.

  • Literatur

  • 1 Liu X, Li Z, Zhang Z. et al. Meta-analysis of GSTM1 null genotype and lung cancer risk in Asians. Med Sci Monit 2014; 20: 1239-1245
  • 2 Lippman SM, Klein EA, Goodman PJ. et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301 (01) 39-51
  • 3 Alpha-Tocopherol Beta. Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994; 330 (15) 1029-1035
  • 4 Satia JA, Littman A, Slatore CG. et al. Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: results from the VITamins And Lifestyle (VITAL) study. Am J Epidemiol 2009; 169 (07) 815-828
  • 5 Chan JM, Darke AK, Penney KL. et al. Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT. Cancer Epidemiol Biomarkers Prev 2016; 25 (07) 1050-1058
  • 6 Martin EM, Fry RC. Environmental influences on the epigenome: exposure-associated DNA Methylation in human populations. Annu Rev Public Health 2018; DOI: doi: 10.1146/annurev-publhealth-040617-014629.
  • 7 Murakami K, Kondo T, Kawase M. et al. Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J Neurosci 1998; 18 (01) 205-213
  • 8 Lee HP, Pancholi N, Esposito L. et al. Early induction of oxidative stress in mouse model of Alzheimer disease with reduced mitochondrial superoxide dismutase activity. PLoS ONE 2012; 7 (01) e28033
  • 9 Wiener HW, Perry RT, Chen Z. et al. A polymorphism in SOD2 is associated with development of Alzheimer’s disease. Genes Brain Behav 2007; 6 (08) 770-776
  • 10 Gamarra D, Elcoroaristizabal X, Fernández-Martínez M. et al. Association of the C47T Polymorphism in SOD2 with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease in Carriers of the APOEε4 Allele. Dis Markers 2015; 2015: 746329
  • 11 Pall ML. Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO-cycle. Med Hypotheses 2007; 69 (04) 821-825
  • 12 Montano MA, da Cruz IB, Duarte MM. Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells. Cytokine 2012; 60 (01) 30-33
  • 13 Lewandowska J, Bartoszek A. DNA methylation in cancer development, diagnosis and therapy -multiple opportunities for genotoxic agents to act as methylome disruptors or remediators. Mutagenesis 2011; 26 (04) 475-487
  • 14 Heyn H, Li N, Ferreira HJ. et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A 2012; 109 (26) 10522-10527
  • 15 Scarpa S, Cavallaro RA, D’Anselmi F. et al. Gene silencing through methylation: an epigenetic intervention on Alzheimer disease. J Alzheimers Dis 2006; 9: 407-414
  • 16 Marcus DL, Thomas C, Rodriguez C. et al. Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Exp Neurol 1998; 150: 40-44
  • 17 Fuso A, Nicolia V, Ricceri L. et al. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Aging Neurobiol. 2012; 33 (07) 1482.e1-16
  • 18 Montgomery SE, Sepehry AA, Wangsgaard JD. et al. The effect of S-adenosylmethionine on cognitive performance in mice: an animal model meta-analysis. PLoS One 2014; 9 (10) e107756
  • 19 Chen H, Liu S, Ji L. et al. Folic acid supplementation mitigates Alzheimer’s disease by reducing inflammation: a randomized controlled trial. Mediators Inflamm 2016 ; 2016:5912146
  • 20 Klein CB, Leszczynska J, Hickey C. et al. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer. Toxicol Appl Pharmacol 2007; 222 (03) 289-297
  • 21 Marshall G, Ferreccio C, Yuan Y. et al. Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst 2007; 99 (12) 920-928
  • 22 Kumagai Y, Sumi D. Arsenic: signal transduction, transcription factor, and biotransformation involved in cellular response and toxicity. Annu Rev Pharmacol Toxicol 2007; 47: 243-262
  • 23 Gebel TW. Genotoxicity of arsenical compounds. Int J Hyg Environ Health 2001; 203 (03) 249-262
  • 24 Hei TK, Filipic M. Role of oxidative damage in the genotoxicity of arsenic. Free Radic Biol Med 2004; 37 (05) 574-581
  • 25 Huang C, Ke Q, Costa M. et al. Molecular mechanisms of arsenic carcinogenesis. Mol Cell Biochem 2004; 255 ( 1–2 ): 57-66