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Lipid peroxidation, free radical production and antioxidant status in breast cancer

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Abstract

Reactive oxygen metabolites (ROMs), including superoxide anion (O2 ·−), hydrogen peroxide (H2O2) and hydroxyl radical (·OH), play an important role in carcinogenesis. There are some primary antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) which protect against cellular and molecular damage caused by the ROMs. We conducted the present study to determine the rate of O2 ·− and H2O2 production, and concentration of malondialdehyde (MDA), as an index of lipid peroxidation, along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients. Forty-two age- and sex-matched patients with minor surgical problems, who had no history of any neoplastic or breast disorders, were taken as controls.

The rate of O2 ·− production was significantly higher (p<0.001) in BC patients than controls, irrespective of clinical stages and menopausal status. Similarly, H2O2 production was significantly higher in BC patients, especially in stage III and postmenopausal groups, as compared to the respective controls. MDA concentration was also observed significantly elevated in stage II (p<0.001), stage III (p<0.01), postmenopausal (p<0.005), and premenopausal (p<0.02) group as compared to their corresponding controls. SOD and GPx activities were found significantly raised in all the groups (p<0.001), except the GPx activity was found a smaller alteration in stage IV (p<0.02). On the contrary, CAT activity was found significantly depressed in all the study groups. The maximum depression was observed in stage II (−61.8%). Lower CAT activity in our study may be the effect of higher production of ROMs, particularly O2 ·− and ·OH. SOD and GPx, however, were less effected by these higher ROMs production. The results of our study have shown a higher ROMs production and decreased CAT activity, which support the oxidative stress hypothesis in carcinogenesis. The relatively higher SOD and GPx may be due to the response of increased ROMs production in the blood. However, the higher SOD and GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the most dangerous ·OH radical followed by MDA. Therefore, administration of CAT may be helpful in the management of BC patients. However, further elaborate clinical studies are required to evaluate the role of such antioxidant enzymes in BC management.

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References

  1. Rao DN, Ganesh B: Estimation of cancer incidence in India in 1991. Ind J Cancer 35: 10–18, 1998

    Google Scholar 

  2. Rao DN, Desai PB, Ganesh B: Epidemiological observation on cancer of the esophagus - a review of Indian studies. Ind J Cancer 33: 55–75, 1996

    Google Scholar 

  3. Oberley LW, berley TD: Free radicals, cancer, and aging. In: Johnson JE Jr, Walford R, Harman D, Miquel J (eds) Free Radicals, Aging and Degenerative Diseases, Alan R Liss, New York, 1986, pp 325–371

    Google Scholar 

  4. Fisher SM, Floyd RA, Copeland ES: Workshop report from the division of research grants, national institute of health. Oxy radicals in carcinogenesis - a chemical pathology study section workshop. Cancer Res 43: 5631–5631, 1983

    Google Scholar 

  5. Chessman KH, and Slater TF: An introduction to free radical biochemistry. British Med Bull 49(3): 481–493, 1993

    Google Scholar 

  6. Babior BM: Oxygen-dependent microbial killing by phagocytes. N Engl J Med 298: 659–725, 1978

    Google Scholar 

  7. Szatrowski TP, Nathan CF: Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 51: 794–798, 1991

    Google Scholar 

  8. Haris C: Individual variation among humans in carcinogen metabolism, DNA adduct formation and DNA repair. Carcinogenesis 10: 1563–1566, 1989

    Google Scholar 

  9. Birnboim HC: DNA strand breakage in human leukocytes exposed to a tumor promoter, phorbol myristate acetate. Science 215: 1247–1249, 1982

    Google Scholar 

  10. Birnboim HC: DNA strand breaks in human leukocytes induced by superoxide anion, hydrogen peroxide and tumor promoters are repaired slowly compared to breaks induced by ionizing radiation. Carcinogenesis 7: 1511–1517, 1986

    Google Scholar 

  11. Lane DP: p53 and human cancers. British Med Bull 50(3): 582–599, 1994

    Google Scholar 

  12. Bos J: The ras gene family and human carcinogenesis. Mutat Res 195: 255–271, 1988

    Google Scholar 

  13. Moraes EC, Keyse SM, Tyrrell RM: The spectrum of mutation generated by passage of a hydrogen peroxide damaged shuttle vector plasmid through a mammalian host. Nucleic Acids Res 17: 8301–8312, 1989

    Google Scholar 

  14. Moraes EC, Keyse SM, Tyrrell RM:Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis. Carcinogenesis 11: 283–293, 1990

    Google Scholar 

  15. Guyton KZ, Kensler TW: Oxidative mechanisms in carcinogenesis. British Med Bull 49: 523–544, 1993

    Google Scholar 

  16. Imlay JA, Chin SM, Linn S: Toxic DNA damages by hydrogen peroxide through the Fanton reaction in vivo and in vitro. Science 240: 640–642, 1988

    Google Scholar 

  17. Baker MA, He S: Elaboration of cellular DNA breaks by hydroperoxides. Free Rad Biol Med 11: 563–572, 1991

    Google Scholar 

  18. Floyd RA: Free Radicals and Cancer. Marcel Dekkor, New York, 1982

    Google Scholar 

  19. Brawn K, Fridovich I: DNA strand scission by enzymatically generated oxygen radicals. Arch Biochem Biophys 206: 414–419, 1981

    Google Scholar 

  20. Cacciuttolo MA, Trinh L, Lumpkin JA, Rao G: Hyperemia induces DNA damage in mammalian cells. Free Rad BiolMed 14: 267–276, 1993

    Google Scholar 

  21. Begleiter A, Blair GM: Quinon-induced DNA damage and its relationship to antitumor activity in L5178Y lymphoblast. Cancer Res 44: 78–82, 1984

    Google Scholar 

  22. Sofni T, Ishidate M Jr: Induction of chromosomal aberrations in cultured Chinese hamster cells superoxide generation system. Mutat Res 140: 27–31, 1984

    Google Scholar 

  23. MacRac WD, Stich HF: Induction of sister-chromatid exchange in Chinese hamster ovary cells by thiol and hydrazine compounds. Mutat Res 68: 351–365, 1979

    Google Scholar 

  24. Freeman BA, Crapo JD: Biology of disease: free radicals and tissue injury. Lab Invest 47: 412–426, 1982

    Google Scholar 

  25. Flohe L, Beckmann R, Giertz H, Loschen G: Oxygen-centered free radicals a mediators of inflammation. Sies H (ed) Oxidative Stress. Academic Press, New York, 1985, pp 405–437

    Google Scholar 

  26. Kensler TW, Bush DM, Kozumbo WJ: Inhibition of tumor promotion by a biomimetic superoxide dismutase. Science 221: 75–77, 1983

    Google Scholar 

  27. Cotgreave I, Moldens P, Orrenius S: Host biochemical defense mechanisms against prooxidants. Annu Rev Pharmacol Toxicol 28: 189–212, 1988

    Google Scholar 

  28. Wendel A: Glutathione peroxidase. In: Jakoby WB, Bend JR, Caldwell J (eds) Enzymatic Basis of Detoxication. Academic Press, New York, 1980, pp 333–348

    Google Scholar 

  29. Hermanek P, Scheibe O, Spiessi B, Wagher G: TNM klassifikation maligner tumoren (UICC) 4. Aukflage, Springer, Berlin, Heidelberg, New York, 1987

    Google Scholar 

  30. Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. A study of 1,409 case of which 359 have been followed for 15 years. Br J Cancer 11: 359–377, 1957

    Google Scholar 

  31. Nishikimi M, Rao AN, Yagi K: The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46: 849–854, 1972

    Google Scholar 

  32. Khan SH, Emerit I, Feingold J: Superoxide and hydrogen peroxide production by macrophage of New Zealand black mice. Free Rad Biol Med 8: 339–345, 1990

    Google Scholar 

  33. Kumari SS, Menon VP: Changes in lipid peroxidation and activities of superoxide dismutase and catalase in isoproterenol induced myocardial infraction in rat. Ind J Exp Biol 25: 419–423, 1989

    Google Scholar 

  34. Misra HP, Fridovich I: The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10): 3170–3175, 1972

    Google Scholar 

  35. Leopold F, Wolfgang AG: Assays of glutathione peroxidase. In: Packer L (ed) Methods in Enzymology. Vol 105, Academic Press, New York, 1984, pp 114–121

    Google Scholar 

  36. Aebi H: Catalase in vitro. In: Packer L (ed) Methods in Enzymology. Vol 105, Academic Press, New York, 1984, pp 121–126

    Google Scholar 

  37. Maxwell SRJ: Prospect for the use of antioxidant therapies. Drug 49(3): 345–361, 1995

    Google Scholar 

  38. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR: DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 89: 3030–3034, 1992

    Google Scholar 

  39. Halliwell B and Gutteridge JMC: Free Radical in Biology and Medicine. Clarendon, Oxford, England, 1985

  40. Fenn WO, Gerschman R, Gilbert DL, Terwilliger DE, Cothran FV: Mutagenic effects of high oxygen tension on Escherichia coli. Proc Natl Acad Sci USA 43: 1027–1032, 1957

    Google Scholar 

  41. Inoue S, Kawanishi S: Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide. Cancer Res 47: 6522–6527, 1987

    Google Scholar 

  42. Pezzano H, Podo F: Structure binary complexes of mono-and polynucleotide with metal ions of the first transitional group. Chem Rev 80: 365–399, 1980

    Google Scholar 

  43. Goldhaber JI, Weiss JN: Oxygen free radicals and cardiac reperfusion abnormalities. Hypertension 20: 118–127, 1992

    Google Scholar 

  44. Yamada T, Grisham MB: Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. Klin Wochensch 69: 988–994, 1991

    Google Scholar 

  45. Schoenberg MH, Buchler M, Beger HG: The role of oxygen radicals in experimental acute pancreatitis. Free Rad Biol Med 12: 515–522, 1992

    Google Scholar 

  46. Goode HF, Webster NR: Free radicals and antioxidants in sepsis. Crit Care Med 21: 1770–1776, 1993

    Google Scholar 

  47. Batra S, Ray G, Singh SK, Kumari S, Ravi RNM, Tandon A: Respiratory disease in children are associated with increased serum free radical scavenging activity. Med Sci Res 26: 357–359, 1998

    Google Scholar 

  48. Liss EA, Videla LA, Gonzatez-Flecha B, Gialivi C, Boveris A: Metabolic regulation in oxidative stress: an overview. In: David JA (ed) Oxidative Damage and Repair. Chemical, Biological and Medical Aspects. Pergamon Press, Oxford, 1991, pp 444–448

    Google Scholar 

  49. Thangaraju M, Vijayakalakshmi T, Sachdanandam P: Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with breast cancer. Cancer 74: 73–82, 1994

    Google Scholar 

  50. Shields P, Harris C: Environmental causes of cancer. Med Clin NA 74: 263–277, 1990

    Google Scholar 

  51. Kumar K, Thangaraju M, Sachdanandam P: Changes observed in antioxidant system in the blood of postmenopausal women with breast cancer. Biochem Int 25: 371–380, 1991

    Google Scholar 

  52. Yueel I, Arpaci F, Berk O: Serum copper and zinc levels and copper/zinc ratio in patients with breast cancer. Biol Tr El 40: 31–38, 1994

    Google Scholar 

  53. Gerber M, Richardson S, Crastes de Paulet P, Crastes de Paule A, Pujol H: Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Nutritional and metabolic aspects. Cancer 64: 2347–2353, 1989

    Google Scholar 

  54. Cunningham ML, Lokesh BR: Superoxide anion generated by potassium superoxide is cytotoxic and mutagenic to Chinese hamster ovary cells. Mutat Res 121: 299–304, 1983

    Google Scholar 

  55. Nagao M, Wakabayashi K, Suwa Y, Kobayashi T: Alteration of mutagenic potentials by peroxidase, catalase, and superoxide dismutase. In: Hartman APE, Kada T, Hollaender A (eds) Antimutagenesis and anticarciogenesis mechanism. Plenum Press, New York, 1986, pp 73–80

    Google Scholar 

  56. Brawn K, Fridovich I: DNA strand scission by enzymatically generated oxygen radicals. Arch Biochem Biophys 206: 414–419, 1981

    Google Scholar 

  57. Iwata K, Shibuya H, Ohkawa Y, Inui N: Chromosomal aberrations in V79 cells induced by superoxide radical generated by the hypoxanthine- xanthine oxidase systems. Toxicol Lett 22: 75–81, 1984

    Google Scholar 

  58. Jones GM, Sanford KK, Parshad R, Gantt R, Price FM, Tarone RE: Influence of added catalase on the chromosome stability and neoplastic transformation of mouse cells in culture. Br J Cancer 52: 583–590, 1985

    Google Scholar 

  59. Saito M, Tannaka N, Ohkawa Y, Inui N: 12-O-tetradecanoylphorbol-13-acetate-enhanced transformation in vitro by radical scavengers. Cancer Lett 35: 167–170, 1987

    Google Scholar 

  60. Escobar JA, Rubio MA, Lissi EA: SOD and catalase inactivation by siglet oxygen and peroxyl radical. Free Rad Biol Med 20(3): 285–290, 1996

    Google Scholar 

  61. Koksoy C, Kavas GO, Akeil E, Koeaturk PA, Kara S, Ozarslan C: Trace element and superoxide dismutase in benign and malignant breast diseases. Breast Cancer Res Treat 45: 1–6, 1997

    Google Scholar 

  62. Weiss SJ, LoBuglio AF: Biology of disease phagocytegenerated oxygen metabolites and cellular injury. Lab Invest 47: 5–18, 1982

    Google Scholar 

  63. Di Ilio C, Sacchetta P, Boccio GD, Rover GL, Federici G: Glutathione peroxidase, glutathione S-transferase and glutathione reductase activities in normal and neoplastic human breast tissue. Cancer Lett 29: 39–42, 1985

    Google Scholar 

  64. Zigman S, Schultz JB, McDaniels T, DeMott M: UV-A damage to lens and antioxidant protection. Photochem Photobiol 61: 91S, 1995

  65. Keno Y, Fridovich I: Superoxide radical inhibits catalase. J Biol Chem 257: 5751–5754, 1975

    Google Scholar 

  66. Piegeolet E, Corbisier P: GPx and SOD and catalase inactivation by AO. Mech Age Dev 51: 283–297, 1990

    Google Scholar 

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Ray, G., Batra, S., Shukla, N.K. et al. Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Res Treat 59, 163–170 (2000). https://doi.org/10.1023/A:1006357330486

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