Molecular Biology Reports

, Volume 38, Issue 6, pp 4101–4109 | Cite as

Cytogenetic study of the effect of Schistosoma mansoni infection on human peripheral blood lymphocytes and the role of β-carotene and vitamin E in modulating this effect

  • Iman A. Khaled
  • Mervat S. El-Ansary
  • Abeya F. Saleh
  • Ola M. Mahmoud
  • Emad A. Baioumi
  • Heba A. Bakr


This study has been made to determine the potential genotoxicity of Schistosoma mansoni on lymphocytes of infected patients using different mutagenic end points. The protective role of antioxidants pro vitamin β-carotene and vitamin E in minimizing these genotoxic effect was also studied. The study focused on the effect of schistosomiasis on the induction of sister chromatid exchange (SCEs) and other chromosomal aberrations. This work was conducted on 24 Schistosoma mansoni infected patients and 10 healthy adults as a control group. Lymphocytes from peripheral blood of patients and control group were used for culture and subsequent cytogenetic studies. The results indicated that schistosomiasis was genotoxic in all examined tests. It induced a significant increase in the percentage of structural chromosomal aberrations and the frequency of SCEs. It also inhibited cell division and caused cell cycle delay. Lymphocyte cultures of S. mansoni patients treated with 10 μg/ml β-carotene or 20 mg/ml vitamin E showed a significant decrease in the percentage of structural chromosomal aberrations and the frequency of SCEs. Schistosomiasis has a genotoxic effect on peripheral blood lymphocytes. The use of the antioxidants β-carotene and vitamin E can be considered a promising approach not only toward inhibiting the genetic damage of schistosomiasis but also as prophylactic agents against infection with S mansoni. Furthermore, higher doses of antioxidant drugs, β-carotene and vitamin E, should be tried as an adjuvants to conventional therapy in a trial to improve treatment of schistosomiasis.


Schistosomiasis β-carotene Vitamin E Chromosomal aberration 


  1. 1.
    Bos D, Mayfield C, Minchella D (2009) Analysis of regulatory protease sequences identified through bioinformatic data mining of the Schistosoma mansoni genome. BMC Genomics 10:488PubMedCrossRefGoogle Scholar
  2. 2.
    Criscione C, Valentim C, Hirai H, LoVerde P, Anderson T (2009) Genomic linkage map of the human blood fluke Schistosoma mansoni. Genome Biol 10:R71PubMedCrossRefGoogle Scholar
  3. 3.
    Bogitish B, Cheng T (1990) Human parasitology. Saunders College publishing, NY, pp 193–210Google Scholar
  4. 4.
    Talaat M, El-Ayyat A, Sayed H, Miller F (1999) Emergence of Schistosoma Mansoni infection in Upper Egypt: the Giza Governorate. Am. J. Trop. Med Hyg 60(5):822–826PubMedGoogle Scholar
  5. 5.
    Osada Y, Kumagai T, Masuda K, Suzuki T, Kanazawa T (2005) Mutagenicity evaluation of Schistosoma spp. extracts by the umu-test and V79/HGPRT gene mutation assay. Parasitol Int 4.1(6):29CrossRefGoogle Scholar
  6. 6.
    Aboul-Ela E (2002) Cytogenetic studies on Nigella sativa seeds extract and thymoquinone on mouse cells infected with schistosomiasis using karyotyping. Mutat Res 516:11–17PubMedGoogle Scholar
  7. 7.
    El-Sharkawy I, Saleh W, El-Alfy N (2003) Cytogenetics of acute and chronic Schistosomiasis mansoni. J Egypt Soc Parasitol 33(2):341–352PubMedGoogle Scholar
  8. 8.
    Bignold L (2009) Mechanisms of clastogen-induced chromosomal aberrations: a critical review and description of a model based on failures of tethering of DNA strand ends to strand-breaking enzymes. Mutat Res 681(2–3):271–298PubMedGoogle Scholar
  9. 9.
    Greenwald P, Mcdonald S (1999) Antioxidants and the prevention of cancer in antioxidants in human health and disease. CABI Publishing, New York, p 213Google Scholar
  10. 10.
    Ifeoma N, Obioma C, Chinyere C.(2009) Effect of vitamin on malondialdehyde and glutathione levels in type 2 diabetic Nigerians. The Int J Pharmacol 7(1)Google Scholar
  11. 11.
    Egesel C, Wong J, Lambert R, Rocheford T (2003) Combining ability of maize inbreds for carotenoids and tocopherols. Crop Sci 43.3(6):818CrossRefGoogle Scholar
  12. 12.
    Reed A, Cho Y, Coombes J, Fassett R (2009) Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients. BMC Nephrol 10:32PubMedCrossRefGoogle Scholar
  13. 13.
    Ashfaq M, Zuberi H, Anwar W (2000) Vitamin E and beta-carotene affect natural killer cell function. Int J Food Sci Nutr 51:13–20CrossRefGoogle Scholar
  14. 14.
    Paiva S, Russell R (1999) Beta-carotene and other carotenoids as antioxidants. J Am Coll Nutr 18:426–433PubMedGoogle Scholar
  15. 15.
    Stahl W, Heinrich U, Jungnann H, Sies H, Tronnier H (2000) Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr 71:795–798PubMedGoogle Scholar
  16. 16.
    Kotake-Nara E, Yonekura L, Nagao A (2010) Effect of glycerophospholipid class on the beta-carotene uptake by human intestinal Caco-2 cells. Biosci Biotechnol Biochem 74(1):209–211PubMedCrossRefGoogle Scholar
  17. 17.
    Ribeiro C, Ramalho A, Lameu E, Da Silva C, David C, Accioly E (2009) Serum concentrations of vitamin A and oxidative stress in critically ill patients with sepsis. Nutr Hosp 24(3):312–317Google Scholar
  18. 18.
    Pongsavee M (2009) Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes. J Occup Med Toxicol 4:27PubMedCrossRefGoogle Scholar
  19. 19.
    Smith E, Costanzo V (2009) Responding to chromosomal breakage during M-phase: insights from a cell-free system. Cell Div 4:15PubMedCrossRefGoogle Scholar
  20. 20.
  21. 21.
    Stevens J, Liu G, Bremer S, Ye K, Xu W, Xu J, Sun Y, Wu G, Savasan S, Krawetz S, Ye C, Heng H (2007) Mitotic cell death by chromosome fragmentation. Cancer Res 67(16):7686–7694PubMedCrossRefGoogle Scholar
  22. 22.
    Shim S, Lee C, Lee J, Shin E, Kyhm J, Park M, Chung S, Cho Y (2007) A De Novo centric fission of chromosome 11 in a patient with recurrent miscarriages. J Korean Med Sci 22:146–148PubMedCrossRefGoogle Scholar
  23. 23.
    Perry P, Wolff S (1974) New Giemsa method for the differential staining of sister chromatids. Nature 251:156–158PubMedCrossRefGoogle Scholar
  24. 24.
    Schneider E, Lewis J (1981) Aging and sister chromatid exchanges. VIII effect of the aging environment on sister chromatid exchanges induction and cell cycle kinetics in Ehrlich ascites tumor cells, a brief note. Mech Ageing Dev 17:327–330PubMedCrossRefGoogle Scholar
  25. 25.
    Kines K, Morales M, Mann V, Gobert G, Brindley P (2008) Integration of reporter transgenes into Schistosoma mansoni chromosomes mediated by pseudotyped murine leukemia virus. FASEB J 22(8):2936–2948PubMedCrossRefGoogle Scholar
  26. 26.
    Shubber E, Salih H (1987) Cytogenetic studies on blood lymphocytes from patients with Schistosoma mansoni. Jpn J Med Sci Biol 40(4):137–145PubMedGoogle Scholar
  27. 27.
    Hamada F, Abdel-Aziz H, Badr F, Moustafa A, Metwally A, Rashad A (1992) The mutagenic effect of praziquantel in S. mansoni infected mice. Arab J Lab 18:301–311Google Scholar
  28. 28.
    Anwar W (1994) Praziquantel (antischistosomal drug): is it clastogenic, co-clastogenic or anticlastogenic? Mutat Res 305:165–173PubMedGoogle Scholar
  29. 29.
    Hagag H (1998) Cytogenetic effect of an organophosphorus insecticide (Cidial) on S. mansoni infected mice. M.Sc. Faculty of Science, Cairo University, EgyptGoogle Scholar
  30. 30.
    Oraby H, Ebeid F, Oraby H (2003) Micronuclei formation in bone marrow cells of mice infected with S. mansoni and the efficacy of Praziquantel treatment. J Egypt Soc Toxicol 28:51–56Google Scholar
  31. 31.
    Huang J, Ma L, Yang F, Fei S, Li L (2008) 45S rDNA Regions are chromosome fragile sites expressed as gaps in vitro on metaphase chromosomes of root-tip meristematic cells in Lolium spp. PLos one 3(5):e2167PubMedCrossRefGoogle Scholar
  32. 32.
    Buchton K Evans H (1973) Methods for the analysis of human chromosome aberrations. World Health Organization, Geneva, pp. 21-22Google Scholar
  33. 33.
    Schinzel A, Schmid W (1976) Lymphocyte chromosome studies in human exposed to chemical mutagens: the validity of the method in 67 patients under cytostatic therapy. Mutat Res 40:139–166PubMedCrossRefGoogle Scholar
  34. 34.
    Brogger A (1982) The chromatid gap- a useful parameter in genotoxicology? Cytogenet Cell Genet 33:14–19PubMedCrossRefGoogle Scholar
  35. 35.
    Ikbal M, Atasoy M, Pirim I, Aliagaoglu C, Karatay S, Erdem T (2006) The alteration of sister chromatid exchange frequencies in Behçet’s disease with and without HLA-B51. J Eur Acad Dermatol Venereol 20(2):149–152PubMedCrossRefGoogle Scholar
  36. 36.
    Shubber E (1987) Sister chromatid exchanges in lymphocytes from patients with S. heamatobium. Mutat Res 180:93–99PubMedGoogle Scholar
  37. 37.
    Toda H, Horaguchi K, Takahashi K, Oikawa A, Matsushima T (1980) EB-virus-transformed human lymphoblasmoid cells for study of sister chromatid exchange and their evaluation as a test system. Cancer Res 40:4775–4779Google Scholar
  38. 38.
    Aboul-Fadl M, Metwalli O (1963) Studies on certain urinary blood serum enzymes in bilharziasis and their possible relation to bladder cancer. Egypt Br J Cancer 15:137–141CrossRefGoogle Scholar
  39. 39.
    Gentile J, Clark D, Aardema M, Johnson M, Blankespoor H (1985) Modification of mutagen metabolism in parasite-infected organism. Arch Environ Health 40:5–12PubMedGoogle Scholar
  40. 40.
    Karska B (1980) Investigations of the mutagenic properties of certain chemical substances during occupational exposure. Po Tyg Lek 35:53–63Google Scholar
  41. 41.
    Fripp P (1966) The histochemical localization of hydrolytic enzymes in schistosomes. In: A Corradetti (ed) Proceedings of the first international congress of Parasitology II, Pregamon, Oxford pp 714–716Google Scholar
  42. 42.
    Bendich A (1999) Immunological role of antioxidant vitamins in: antioxidants in human health and disease. CABI Publishing, New York, pp 213Google Scholar
  43. 43.
    Berhe N, Halvorsen B, Gundersen T, Myrvang B, Gundersen S, Blomhoff R (2007) Reduced serum concentrations of retinol, α-tocopherol, high concentrations of hydroperoxide are associated with community levels of S. mansoni infection and schistosomal periportal fibrosis in Ethiopian school children. Am J Trop Med Hyg 76(5):943–949PubMedGoogle Scholar
  44. 44.
    Seif el-Din S, El-Lakkany N, Hagag H, Ebeid F (2010) Role of β-carotene and N-Acetyl-L Cysteine with and without Praziquantel treatment in modulating Schistosoma mansoni-induced genotoxic effects on Albino mice. Res J Med Med Sci 5(1):8–17Google Scholar
  45. 45.
    Zalata K, Nasif W, Ming S, Lotfy M, Nada N, El-Hak N, Leech S (2005) p53, Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis. Egypt Cell Oncol 27(4):245–253Google Scholar
  46. 46.
    Glei M, Liegibel U, Ebert M, Bohm V, Pool-Zobel B (2002) Beta-carotene reduces bleomycin-induced genetic damage in human lymphocytes. Toxicol Appl Pharmacol 179(2):65–73PubMedCrossRefGoogle Scholar
  47. 47.
    Ahmad S, Hoda A, Afzal M (2002) Additive action of vitamins C and E against hydrocortisone-induced genotoxicity in human lymphocyte chromosomes. Int J Vitam Nutr Res 72:204–209PubMedCrossRefGoogle Scholar
  48. 48.
    Abid-Essefi S, Baudrimont I, Hassen W, Ouanes Z, Mobio T, Anane R, Creppy E, Bacha H (2003) DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in cultured DOK, Vero and Caco-2 cells: prevention by Vitamin E. Toxicology 192:237–248PubMedCrossRefGoogle Scholar
  49. 49.
    Schneider M, Diemer K, Engelhart K, Zankl H, Trommer W, Biesalski H (2001) Protective effects of vitamins C and E on the number of micronuclei in lymphocytes in smokers and their role in ascorbate free radical formation in plasma. Free Rad Res 34(3):209–219CrossRefGoogle Scholar
  50. 50.
    Zhang J, Zhao Y, Shi H (2001) Effect of beta-carotene and vitamin C on the expression of c-myc in human leukemic cell. Wei Sheng Yan Jiu 30:160–162PubMedGoogle Scholar
  51. 51.
    Mkoji G, Smith J, Prichard R (1988) Antioxidant systems in Schistosoma mansoni: correlation between susceptibility to oxidant killing and the levels of scavengers of hydrogen peroxide and oxygen free radicals. Int J Parasitol 18:661–666PubMedCrossRefGoogle Scholar
  52. 52.
    Nare B, Smith J, Prichard R (1990) Schistosoma mansoni: levels of antioxidants and resistance to oxidants increase during development. Exp Parasitol 70:389–397PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Iman A. Khaled
    • 1
  • Mervat S. El-Ansary
    • 2
  • Abeya F. Saleh
    • 1
  • Ola M. Mahmoud
    • 1
  • Emad A. Baioumi
    • 3
  • Heba A. Bakr
    • 4
  1. 1.Department of HaematologyTheodor Bilharz Research InstituteGizaEgypt
  2. 2.Department of ImmunologyCairo UniversityGizaEgypt
  3. 3.Department of HepatologyTheodor Bilharz Research InstituteGizaEgypt
  4. 4.Department of ScienceEin Shams UniversityCairoEgypt

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