Green Tea Polyphenol Protection Against 4-Nitroquinoline 1-Oxide-Induced Bone Marrow Lipid Peroxidation and Genotoxicity in Wistar Rats

  • Pandurangan, Ashok Kumar ;
  • Periasamy, Srinivasan ;
  • Anandasadagopan, Suresh Kumar ;
  • Ganapasam, Sudhandiran ;
  • Srinivasalu, Shyamala Devi Chennam
  • Published : 2012.08.31


4-Nitroquinoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, has been found to induce lipid peroxidation in vivo and in vitro. Green tea contains a high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GTP) might be expected play a protective role against 4-NQO induced lipid peroxidation and bone marrow toxicity. In the present study, a dose of 200 mg of GTP/kg b.wt/day was given orally for a week, simultaneously animals received 0.2 ml of 0.5% 4-NQO in propylene glycol (5 mg/ml) injected intramuscularly for three times/week. Oxidants and antioxidants such as malendialdehyde (MDA) and thiols, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased in 4-NQO induced animals except MDA, and these parameters were brought back to near normalcy on treatment with GTP. The results suggest that GTP treatment offers significant protection against 4-NQO induced lipid peroxidation and bone marrow toxicity and might be a promising potential candidate for prevention of mutations leading to cancer.


Green tea polyphenols;4-nitroquinoline 1-oxide;bone marrow;lipid peroxidation


  1. Aceto A, Di Ilio C, Lo BM, et al (1990). Differential activity of human, rat, mouse and bacteria glutathione transferase isoenzymes towards 4-nitroquinoline 1-oxide. Carcinogenesis, 11, 2267-9.
  2. Anderson RF, Amarasinghe C, Fisher LJ, et al (2000). Reduction in free-radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids. Free Radic Res, 33, 91-103.
  3. Bailleul B, Daubersies P, Galiegue-Zouitina S, Loucheux- Lefebvre MH (1989). Molecular basis of 4-nitroquinoline 1-oxide carcinogenesis. Jpn J Cancer Res, 80, 691-7.
  4. Bellomo G, Mirabelli F, Richelmi P, Orrenius S (1983). Critical role of sulphydryl groups in ATP- dependent $Ca^{2+}$ sequestration by the plasma membrane fraction from rat liver. FEBS Lett, 163, 136-9.
  5. Benson AM (1993). Conversion of 4-nitroquinoline 1-oxide (4NQO) to 4-hydroxyaminoquinoline 1-oxide by a dicumarol resistant hepatic 4NQO nitroreductase in rats and mice. Biochem Pharmacol, 46, 1217-21.
  6. Booth DR (1990). A relationship found between intra-oral sites of 4NQO reductase activity and chemical carcinogenesis. Cell Tissue Kinet, 23, 331-40.
  7. Casini AF, Maellaro E, Pompella A, et al (1987). Lipid peroxidation, protein thiols and calcium homeostasis in bromobenzene induced liver damage. Biochem Pharmacol, 36, 3689.
  8. Cederbaum AI, Cohen G (1984). In: Methods in enzymology. Packer L. editor Academic press, San Diego, 105, 516-22.
  9. Cerutti PA (1994). Oxyradicals and cancer. Lancet, 344, 862-8.
  10. Creighton TE (1983). Biochemical, physiological, toxicological and clinical aspects, In: A. Larsson, S. Orrenins, A. Holmgren, B Mannervik (Ed.), Function of glutathione, Raven press, New York, pp. 205-213.
  11. Cochrane CG (1991). Cellular injury by oxidants. Am J Med, 91, 23.
  12. Eveson JW (1981). Animal models of intra-oral chemical carcinogenesis: a review. J Oral Pathol, 10, 129-46.
  13. Fann YC, Metosh-Dickey CA, Winston GW, (1999). Enzymatic and non-enzymatic production of free radicals from the carcinogens 4-nitroquinoline N-oxide and 4-hydroxylaminoquinoline N-oxide. Chem Res Toxicol, 12, 450-8.
  14. Feron VJ, Tie HP, De Vrjer F, et al (1991). Aldehydes: occurrence, carcinogenic potential mechanism of action and risk assessment. Mutat Res, 259, 362-6.
  15. Fields WR, Li Y, Townsend AJ (1994). Protection by transfected glutathione S-transferase isozymes against carcinogen induced alkylation of cellular macromolecules in human MCF-7 cells. Carcinogenesis, 15, 1155-60.
  16. Fisker AV (1990). Experimental oral carcinogenesis. A basic rat model for the study of oral carcinogenesis using the carcinogen 4-nitroquinoline1-oxide. Dan Med Bull, 37, 433-42.
  17. Goth-Goldstein R, Tincknell BP, Hughes M (1984). Toxicity of 4-nitroquinoline 1-oxide in Chinese hamster ovary cells: influence of cell density and of position in the cell cycle. Mutat Res, 140, 209-13.
  18. Griffith OW (1980). Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem, 106, 207-12.
  19. Gupta SK, Halder N, Srivastava S, et al (2002). Green tea (Camellia sinensis) protects against selenite-induced oxidative stress in experimental cataractogenesis. Ophthalmic Res, 34, 258-63.
  20. Habig WH, Pabst MJ, Jacoby BW (1974). Glutathione S transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem, 249,1730-7.
  21. Halliwell B, Murcia MA, Chirico S, Aruoma OI (1995). Free radicals and antioxidants in food and in vivo: what they do and how they work. Crit Rev Food Sci Nutr, 35, 7-20.
  22. Hendler FJ, Yuan B, Oechlsi MN (1996). 4-NQO oral carcinogenesis, a murine model of human head and neck cancer. Head Neck Cancer, ?, 79-87.
  23. Irshad M, Chaudhuri PS (2002). Oxidant-antioxidant system: Role and significance in human body. Indian J Exp Biol 40, 1233-1239.
  24. Isbrucker RA, Bausch J, Edwards JA, Wolz E (2006). Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: Genotoxicity. Food Chem Toxicol, 44, 626-35.
  25. Ito N (1981). In vivo carcinogenesis of 4-nitroquinoline 1-oxide and related compounds. Carcinog Compr Surv, 6, 117-53
  26. Jankun J, Selman SH, Swiercz R, Skrzypczak-Jankun E (1997). Why drinking green tea could prevent cancer. Nature, 387, 561.
  27. Katiyar SK, Mukhtar H (1996). Tea in chemoprevention of cancer; epidemiological and experimental studies. Int J Oncol, 8, 221-38.
  28. Koch CJ, Stobbe CC, Hettiaratchi P (1989). Combined radiation protective and radiation sanitizing agents: IV. Measurement of intracellular protector concentrations. Int J Radiat Oncol Biol Phys, 16, 1025-7.
  29. Misra HP, Fridovich I (1972). The role of superoxide anion in the auto oxidation of epinephrine and a simple assay of superoxide dismutase. J Biol Chem, 247, 3170-5.
  30. Moron MS, Depierre JW, Mannervik B (1979). Levels of glutathione, glutathione reductase and glutathione-Stransferase activities in rat lung and liver. Biochim Biophys Acta, 582, 67-78.
  31. Nunoshiba T, Demple B (1993). Potent intracellular oxidative stress exerted by the carcinogen 4-nitroquinoline-N-oxide. Cancer Res, 53, 3250-2.
  32. Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-8.
  33. Ramotar D, Belanger E, Brodeur I, et al (1998). A yeast homologue of the human phosphotyrosyl phosphatase activator PTPA is implicated in protection against oxidative DNA damage induced by the model carcinogen 4-nitroquinoline 1-oxide. J Biol Chem, 273, 21489-96.
  34. Ray G, Husian SA (2002). Oxidant, antioxidants and carcinogenesis, Indian J Exp Biol, 40, 1213-2.
  35. Rotruck JT, Pope AL, Ganther HE, et al (1973). Selenium : biochemical rote as a component of Glutathione peroxidase. Science, 179, 588-90.
  36. Sedlak J, Lindsay RH (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem, 25, 192-205.
  37. Srinivasan P, Sabitha KE, Shyamaladevi CS (2004). Therapeutic efficacy of green tea polyphenols on cellular thiols in 4-Nitroquinoline 1-oxide induced oral carcinogenesis. Chem Biol Inter, 149, 81-7.
  38. Srinivasan P, Sabitha KE, Shyamaladevi CS (2006). Modulatory efficacy of green tea polyphenols on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide-induced oral carcinogenesis-A therapeutic approach. Chem Biol Interact, 162, 149-56
  39. Srinivasan P, Sabitha KE, Shyamaladevi CS (2007). Attenuation of 4-Nitroquinoline 1-oxide induced in vitro lipid peroxidation by green tea polyphenols. Life Sci, 12, 1080-6.
  40. Staal GEJ, Visser J, Veeger C (1969). Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta, 185, 39-48.
  41. Takahara S, Hamilton BH, Nell JV, et al (1960). Hypocatalasemia, a new genetic carrier state. J Clin Invest, 29, 610-9.
  42. Tsuda H (1990). Role of DT diaphorase the cytotoxicity of menadione and 4-nitroquinoline-1-oxide in cultured mammalian fibroblastic cells. Cancer Lett, 55, 195-9.
  43. Upsani CD, Khera A, Balaraman R (2001). Effect of Lead and vitamin E, C or spiruline on malondialdehyde, conjucated dienes and hydroperoxides in rats. Ind J Exp Biol, 39, 70-4.
  44. Vaca CE, Wilhelm J, Harms-Rihsdash M (1998). Interaction of lipid peroxidation product with DNA. Mutat Res Rev Genet Toxicol, 195, 137.
  45. Varnes ME, Biaglow JE (1979). Interactions of the carcinogen 4-nitroquinoline 1-oxide with the non-protein thiols of mammalian cells. Cancer Res, 39, 2960-5.
  46. Walker IG, Sridhar R (1976). The formation and repair of singlestrand breaks in DNA of cultured mammalian cells treated with UV-light, methylating agents or 4-nitroquinoline-1- oxide. Chem Biol Interact, 12, 229-39.
  47. Yamamoto K, Inoue S, Kawanishi S (1993). Site-specific DNA damage and 8-hydroxydeoxyguanosine formation by hydroxylamine and 4-hydroxyaminoquinoline 1-oxide in the presence of Cu(II): role of active oxygen species. Carcinogenesis, 14, 1397-401.
  48. Yu R, Jiao JJ, Duh JL, et al (1997). Activation of mitogenactivated protein kinases by green tea polyphenols: potential signaling pathways in the regulation of antioxidantresponsive element-mediated phase II enzyme gene expression. Carcinogenesis, 18, 451-6.
  49. Zhang Y, Chen SY, Hsu T, Santella RM (2002). Immunohistochemical detection of malondialdehyde-DNA adducts in human oral mucosa cells. Carcinogenesis, 23, 207-11.

Cited by

  1. Luteolin, a Bioflavonoid, Attenuates Azoxymethane-Induced Effects on Mitochondrial Enzymes in Balb/c Mice vol.14, pp.11, 2013,
  2. Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways vol.14, pp.4, 2013,
  3. Pu-erh Tea Powder Preventive Effects on Cisplatin-Induced Liver Oxidative Damage in Wistar Rats vol.15, pp.17, 2014,