Ukr.Biochem.J. 2018; Volume 90, Issue 3, May-Jun, pp. 5-16

doi: https://doi.org/10.15407/ubj90.03.005

Biochemical mechanisms of free-radical damage to the nuclear genome by cadmium

23.04.2018   Uncategorized   No comments

I. M. Trakhtenberg1, Y. I. Gubsky2, E. L. Levitsky3, I. F. Belenichev4

1Institute of Occupational Medicine, National Academy of Medical Sciences of Ukraine, Kyiv;
2Insitute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv;
3Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: levitsky@biochem.kiev.ua;
4Zaporozhye State Medical University of the Ministry of Health of Ukraine

Cadmium, has been used for many years in industry and agriculture. Its active use is associated with a danger to human health due to a significant toxic effect on the body. The purpose of the review was to analyze the literature data and the results of our own experimental research on the biochemical mechanisms of the toxic effect of cadmium on the nuclear chromatin of cells, primarily the liver. Based on this analysis, the concept that the toxicity of cadmium is associated with damage caused by cadmium-induced free radicals was confirmed. The reactive oxygen species formed in this way are active damaging agents that cause toxic effects, including mutagenic, which ultimately leads to apoptosis and cell death.

Keywords: , , ,

References:

  1. Trakhtenberg IM. A book about poisons and poisonings. Essays on toxicology. Kiev: Naukova Dumka, 2000. 368 p.
  2. Trakhtenberg IM, Levitsky EL. Prophylactic toxicology in Ukraine: time link in solving current problems. Environ Health. 2006;39(4):3-8.
  3. Trakhtenberg IМ, Levitsky EL. Genetic toxicology. In: Genetic Medicine. Publ.: Odessa Med. Univ., 2008: 183-221.
  4. Elinder CG. Cadmium as an environmental hazard. IARC Sci Publ. 1992;(118):123-32. PubMed
  5. Hengstler JG, Bolm-Audorff U, Faldum A, Janssen K, Reifenrath M, Götte W, Jung D, Mayer-Popken O, Fuchs J, Gebhard S, Bienfait HG, Schlink K, Dietrich C, Faust D, Epe B, Oesch F. Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected. Carcinogenesis. 2003 Jan;24(1):63-73. PubMed, CrossRef
  6. Fojtová M., Kovařík A. Genotoxic effect of cadmium is associated with apoptotic changes in tobacco cells. Plant Cell Environ. 2000;23(5):531–537.  CrossRef
  7. ABMS, 1994. Non-ferrous metal data, cadmium. American Bureau of Metal Statistic Inc. Secaucus, New Jersey.
  8. Mirsalis JC, Butterworth BE. Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: an in vivo — in vitro assay for potential carcinogens and mutagens. Carcinogenesis. 1980 Jul;1(7):621-5. PubMed, CrossRef
  9. Muntau H, Baudo R. Sources of cadmium, its distribution and turnover in the freshwater environment. IARC Sci Publ. 1992;(118):133-48. PubMed
  10. Nair AR, Degheselle O, Smeets K, Van Kerkhove E, Cuypers A. Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)? Int J Mol Sci. 2013 Mar 18;14(3):6116-43. PubMed, PubMedCentral, CrossRef
  11. Thornton I. Sources and pathways of cadmium in the environment. IARC Sci. Publ. 1992; 118: 149–162.
  12. Llewellyn TO. Cadmium. Minerals Yearbook. Bureau of mines. U.S. Department of the Interior. 1988; 1: 191-195.
  13. EPA, 1988. Health effects assessment for cadmium. Cincinnati: OH. U. S. Environmental Protection Agency, Environmental Criteria and Assessment Office. EPA/600/8-89/087. NTIS no. PB90 – 142399.
  14. IARC, 1993. Cadmium and certain cadmium compounds. In: IARC monographs of the evaluation of carcinogenic risk of chemicals to humans. Beryllium, cadmium, mercury and exposure in the glass manufactory industry. IARC monographs 58. P. 119–146, 210–236.
  15. NTP, 1991. Cadmium and certain cadmium compounds. In: Seventh Annual Report on Cancirogens, Summary 1991. U. S. National Toxicology Program. U. S. Public Health Service, Department of Health and Human Services. P. 114‒121.
  16. Kundiev YuI, Trakhtenberg IM. Chemical safety in Ukraine. Kiev: Avicenna, 2007. 72 p.
  17. Toxicological Profile for Cadmium (Draft for Public Comment. Comment Periods Ends: February 17, 1998), U. S. Department of Health and Human Services. Public Health Service. Agency for toxic substances and disease registry. September 1997. 347 p.
  18. Trakhtenberg IM, Tychinin VA, Talakin YuI. On the problem of carrier of heavy metals. Zhurn Akad Med Nauk Ukraine. 1999;5(1):87-95.
  19. Waalkes MP, Oberdorster G. Cadmium Carcinogenesis. Foulkes E. C., ed. Metal carcinogenesis. Bosa Raton: CRC Press, 1990.
  20. Waalkes MP, Wahba ZZ, Rodrigues RE. Cadmium. Hazardous Materials Toxicology. Clinical Principles of Environmental Health. Eds. J. B. Sullivan, G. R. Krieger. Williams and Wilkins. 1992, P. 845–852.
  21. Stowe HD, Wilson M, Goyer RA. Clinical and morphologic effects of oral cadmium toxicity in rabbits. Arch Pathol. 1972 Nov;94(5):389-405. PubMed
  22. Cárdenas A, Bernard A, Lauwerys R. Incorporation of [35S]sulfate into glomerular membranes of rats chronically exposed to cadmium and its relation with urinary glycosaminoglycans and proteinuria. Toxicology. 1992 Dec 4;76(3):219-31. PubMed, CrossRef
  23. Cárdenas A, Ramis I, Hotter G, Roselló J, Gelpí E, Roels H, Bernard A, Lauwerys R. Human and experimental studies on renal eicosanoid response to long-term cadmium exposure. Toxicol Appl Pharmacol. 1992 Oct;116(2):155-60. PubMed, CrossRef
  24. Roels H, Bernard AM, Cárdenas A, Buchet JP, Lauwerys RR, Hotter G, Ramis I, Mutti A, Franchini I, Bundschuh I. Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium. Br J Ind Med. 1993 Jan;50(1):37-48. PubMed, PubMedCentral, CrossRef
  25. Friberg L. Health hazards in the manufacture of alkaline accumulators with special reference to chronic cadmium poisoning; a clinical and experimental study. Acta Med Scand Suppl. 1950;240:1-124. PubMed
  26. Bonnell JA. Emphysema and proteinuria in men casting copper-cadmium alloys. Br J Ind Med. 1955 Jul;12(3):181-95. PubMed, PubMedCentral, CrossRef
  27. Adams RG, Harrison JF, Scott P. The development of cadmium-induced proteinuria, impaired renal function, and osteomalacia in alkaline battery workers. Q J Med. 1969 Oct;38(152):425-43. PubMed, CrossRef
  28. Glaser U, Klöppel H, Hochrainer D. Bioavailability indicators of inhaled cadmium compounds. Ecotoxicol Environ Saf. 1986 Jun;11(3):261-71. PubMed, CrossRef
  29. Oldiges H, Glaser U. The inhalative toxicity of different cadmium compounds in rats. Trace Elem Med. 1986;3:72–75.
  30. Kutzman RS, Drew RT, Shiotsuka RN, Cockrell BY.  Pulmonary changes resulting from subchronic exposure to cadmium chloride aerosol. J Toxicol Environ Health. 1986;17(2-3):175-89. PubMed, CrossRef
  31. Gill KD, Pal R, Nath R. Effect of cadmium on lipid peroxidation and antioxidant enzymes in undernourished weanling rat brain. Pharmacol Toxicol. 1989 Jul;65(1):73-7. PubMed, CrossRef
  32. Gill KD, Pal R, Sandhir R. Effect of chronic cadmium exposure on lipid composition and peroxidation in liver and kidneys in rats. Med Sci Res. 1989; 17: 921-924.
  33. Jamall IS, Smith JC. Effects of cadmium on glutathione peroxidase, superoxide dismutase, and lipid peroxidation in the rat heart: a possible mechanism of cadmium cardiotoxicity. Toxicol Appl Pharmacol. 1985 Aug;80(1):33-42. PubMed, CrossRef
  34. Liu J, Qu W, Kadiiska MB. Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol. 2009 Aug 1;238(3):209-14.  PubMed, PubMedCentral, CrossRef
  35. Gubsky YuI, Levitsky EL, Lenchevskaia LK, Vistunova IE. Effect of cadmium chloride on DNA-, RNA-polymerase activity and lipid peroxidation of chromatin fraction in rat liver. Ukr Biokhim Zhurn. 1993 Sep-Oct;65(5):112-5. (In Russian). PubMed
  36. Gubsky YuI. Cell death: free radicals, necrosis, apoptosis. Vinnytsia, 2015. 360 p.
  37. Gobe G, Crane D. Mitochondria, reactive oxygen species and cadmium toxicity in the kidney. Toxicol Lett. 2010 Sep 15;198(1):49-55.  PubMed, CrossRef
  38. Minchenko OH, Tsymbal DO, Minchenko DO, Ratushna OO. The role of the TNF receptors and apoptosis inducing ligands in tumor growth. Ukr Biochem J. 2016 Sep-Oct;88(5):18-37.  PubMed, CrossRef
  39. Kitamura M, Hiramatsu N. The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity. Biometals. 2010 Oct;23(5):941-50. PubMed, CrossRef
  40. Gubsky YuI, Levitsky EL. Peroxide-antioxidant mechanism of regulation of chromatin activity. Zhurn Akad Med Nauk Ukraine. 1997;3(2):275-281.
  41. Gubsky YuI, Levitsky EL. Mechanisms of the lipid peroxidation of the liver rats chromatin fractions. Biopolym Cell. 1993;9(5):34-43.  CrossRef
  42. Levitsky EL, Gubsky YuI. Free radical damage of the nuclear genetic apparatus of cells. Ukr Biokhim Zhurn. 1994 Jul-Aug;66(4):18-30. (In Russian). PubMed
  43. Gubsky YuI, Levitsky EL, Volkov GL. Fatty acid composition of rat liver chromatin fractions under conditions of stimulation of lipid peroxidation. Ukr Biokhim Zhurn. 1991 Jan-Feb;63(1):87-91. (In Russian). PubMed
  44. Gubsky YuI, Levitsky EL, Primak RG, Golubov MI, Novikova SN. Conformational characteristics and packing of endogenous lipid fractions of transcriptionally active and repressed chromatin. Ukr Biokhim Zhurn. 1991 Mar-Apr;63(2):83-9. (In Russian). PubMed
  45. Morselt AF, Leene W, De Groot C, Kipp JB, Evers M, Roelofsen AM, Bosch KS. Differences in immunological susceptibility to cadmium toxicity between two rat strains as demonstrated with cell biological methods. Effect of cadmium on DNA synthesis of thymus lymphocytes. Toxicology. 1988 Feb;48(2):127-39. PubMed, CrossRef
  46. Gubskii YuI, Levitskii EL, Gol’dshtein NB, Litoshenko AYa. Lipid peroxidation and the endogenous DNA polymerase activity of fractions of isolated liver chromatin in rats. Biull Eksp Biol Med. 1989 Mar;107(3):296-8. (In Russian). PubMed, CrossRef
  47. Meena Bai M, Divya K, Haseena Bhanu SK, Sailaja G, Sandhya D, Thyagaraju K. Evaluation of Genotoxic and Lipid Peroxidation Effect of Cadmium in Developing Chick Embryos. J Environ Anal Toxicol. 2014; 4(6):238. CrossRef
  48. Azza A. Ashmawy,  Mohammed A. Rashed,  Aiman H. Atta, Amr G. Ibrahim, Fagr Kh. Abdel-Gawad. Genotoxic Effect of Cadmium on Nile Tilapia (Oreochromis niloticus). Int J Sci Eng Res. 2015; 6(8):971-978.
  49. Sarkar A, Bhagat J, Ingole BS, Rao DP, Markad VL. Genotoxicity of cadmium chloride in the marine gastropod Nerita chamaeleon using comet assay and alkaline unwinding assay. Environ Toxicol. 2015 Feb;30(2):177-87.  PubMed, CrossRef
  50. Schwerdtle T, Ebert F, Thuy C, Richter C, Mullenders LH, Hartwig A. Genotoxicity of soluble and particulate cadmium compounds: impact on oxidative DNA damage and nucleotide excision repair. Chem Res Toxicol. 2010 Feb 15;23(2):432-42. PubMed, CrossRef
  51. Jindal R, Verma S. In vivo genotoxicity and cytotoxicity assessment of cadmium chloride in peripheral erythrocytes of Labeo rohita (Hamilton). Ecotoxicol Environ Saf. 2015 Aug;118:1-10.  PubMed, CrossRef
  52. Hartmann A, Elhajouji A, Kiskinis E, Poetter F, Martus H, Fjällman A, Frieauff W, Suter W. Use of the alkaline comet assay for industrial genotoxicity screening: comparative investigation with the micronucleus test. Food Chem Toxicol. 2001 Aug;39(8):843-58. PubMed, CrossRef
  53. Filipic M, Fatur T, Vudrag M. Molecular mechanisms of cadmium induced mutagenicity. Hum Exp Toxicol. 2006 Feb;25(2):67-77. PubMed, CrossRef
  54. Gosslau A, Rensing L. Oxidative stress, age-dependent [correction of age-related] cell damage and antioxidative mechanisms. Z Gerontol Geriatr. 2002 Apr;35(2):139-50. PubMed,  CrossRef
  55. Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez-Ruiz MC. Liver and Cadmium Toxicity. J Drug Metab Toxicol. 2012; S5:001.    CrossRef
  56. Hu KH, Li WX, Sun MY, Zhang SB, Fan CX, Wu Q, Zhu W, Xu X. Cadmium Induced Apoptosis in MG63 Cells by Increasing ROS, Activation of p38 MAPK and Inhibition of ERK 1/2 Pathways. Cell Physiol Biochem. 2015;36(2):642-54. PubMed, CrossRef
  57. Rani A, Kumar A, Lal A, Pant M. Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res. 2014 Aug;24(4):378-99.  PubMed, CrossRef
  58. Madejczyk MS, Baer CE, Dennis WE, Minarchick VC, Leonard SS, Jackson DA, Stallings JD, Lewis JA. Temporal changes in rat liver gene expression after acute cadmium and chromium exposure. PLoS One. 2015 May 19;10(5):e0127327. PubMed, PubMedCentral, CrossRef
  59. Zhou ZH, Lei YX, Wang CX. Analysis of aberrant methylation in DNA repair genes during malignant transformation of human bronchial epithelial cells induced by cadmium. Toxicol Sci. 2012 Feb;125(2):412-7.  PubMed, CrossRef
  60. Fernández EL, Gustafson AL, Andersson M, Hellman B, Dencker L. Cadmium-induced changes in apoptotic gene expression levels and DNA damage in mouse embryos are blocked by zinc. Toxicol Sci. 2003 Nov;76(1):162-70. PubMed, CrossRef
  61. Skipper A, Sims JN, Yedjou CG, Tchounwou PB. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress. Int J Environ Res Public Health. 2016 Jan 2;13(1). pii: E88.  PubMed, PubMedCentral, CrossRef
  62. Nemmiche S, Chabane-Sari D, Kadri M, Guiraud P. Cadmium chloride-induced oxidative stress and DNA damage in the human Jurkat T cell line is not linked to intracellular trace elements depletion. Toxicol In Vitro. 2011 Feb;25(1):191-8.  PubMed, CrossRef
  63. Mallya R, Chatterjee PK, Vinodini NA, Chatterjee P, Mithra P. Moringa oleifera Leaf Extract: Beneficial Effects on Cadmium Induced Toxicities – A Review. J Clin Diagn Res. 2017 Apr;11(4):CE01-CE04. PubMed, PubMedCentral, CrossRef
  64. Błasiak J. DNA-Damaging Effect of Cadmium and Protective Action of Quercetin. Pol J Environ Stud. 2001; 10(6):437–442.
  65. Park JY, Seo YR. The protective role of Nrf2 in cadmium-induced DNA damage. Mol Cell Toxicol. 2011; 7(1):61‒66. CrossRef
  66. Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 2003 Jul;17(10):1195-214. PubMed, CrossRef
  67. Bertin G, Averbeck D.Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie. 2006 Nov;88(11):1549-59. PubMed, CrossRef
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