The Environmental and Human Effects of Ptaquiloside-Induced Enzootic Bovine Hematuria: A Tumorous Disease of Cattle

Chapter
Part of the Reviews of Environmental Contamination and Toxicology book series (RECT, volume 224)

Abstract

Enzootic bovine hematuria (EBH) is a disease of cattle that is characterized by the intermittent presence of blood in urine caused by malignant lesions in the urinary bladder. The disease causes anemia, progressive emaciation, and death (Jones and Hunt 1983; Hopkins 1986). This neoplastic disease is primarily caused by chronic ingestion of ferns, and affliction with the papillomavirus is often associated with it (Campo et al. 1992; Campo 1997; Santos et al. 1998). A decade ago, a comprehensive review of this disease was published by Dawra and Sharma (2001). In this review, we provide an update on the various aspects of EBH and include an assessment of the effect of consuming these disease-inducing ferns on both animal and human health, and the associated environmental implications.

Keywords

Hydrolysis Adenocarcinoma Glutathione Adenoma Respiration 

References

  1. Agnew MP, Lauren DR (1991) Determination of ptaquiloside in Bracken fern (Pteridium esculentum). J Chromatogr 538:462–468Google Scholar
  2. Alonso-Amelot ME (1997) The link between bracken fern and stomach cancer: milk. Nutrition 13:694–696Google Scholar
  3. Alonso-Amelot ME, Avendano M (2002) Human carcinogenesis and bracken fern: a review of the evidence. Curr Med Chem 9:675–686Google Scholar
  4. Alonso-Amelot ME, Rodulfo-Baechler S, Jaimes-Espinosa R (1995) Comparative dynamics of ptaquiloside and pterosin B in the two varieties (caudatum and arachnoideum) of neotropical bracken fern (P. aquilinum L. Kuhn). Biochem Syst Ecol 23:709–716Google Scholar
  5. Alonso-Amelot ME, Castillo U, Smith BL, Lauren DR (1998) Excretion, through milk, of ptaquiloside in bracken-fed cows—a quantitative assessment. Lait 78:413–423Google Scholar
  6. Aparecida da Silva M, Scardua CM, Dorea MD, Carvalho NL, Martins IVF, Donatele DM (2009) Prevalence of bovine enzootic haematuria in dairy cattle in the Caparao microregion, southern Espirito Santo, between 2007 and 2008. Ciencia Rural, Santa Maria 39:1847–1850Google Scholar
  7. Ayala-Luis KB, Hansen PB, Rasmussen LH, Hansen HCB (2006) Kinetics of ptaquiloside hydrolysis in aqueous solution. Environ Toxicol Chem 25:2623–2629Google Scholar
  8. Balcos LGF, Borzacchiello G, Russo V, Popescu O, Roperto S, Roperto F (2008) Association of bovine papillomavirus type-2 and urinary bladder tumours in cattle from Romania. Res Vet Sci 85:145–148Google Scholar
  9. Balmain A, Brown K (1988) Oncogene activation in chemical carcinogenesis. Adv Cancer Res 51:147–182Google Scholar
  10. Barbacid M (1986) Oncogenes and human cancer: cause or consequence? Carcinogenesis 7:1037Google Scholar
  11. Basaran AA, Yu T-W, Plewa MJ, Anderson D (1996) An investigation of some Turkish herbal medicines in Salmonella typhimurium and in the comet assay in human lymphocytes. Teratog Carcinog Mutagen 16:125–138Google Scholar
  12. Borzacchiello G, Ambrosio V, Galati P, Perillo A, Roperto F (2003a) Cyclooxygenase-1 and -2 expression in urothelial carcinomas of the urinary bladder in cows. Vet Pathol 40:455–459Google Scholar
  13. Borzacchiello G, Iovane G, Marcante ML, Poggiali F, Roperto F, Roperto S, Venuti A (2003b) Presence of BPV-2 DNA and expression of the viral oncoprotein E5 in naturally occurring bladder tumours in cows. J Gen Virol 84:2921–2926Google Scholar
  14. Borzacchiello G, Russo V, Spoleto C, Roperto S, Balcos L, Rizzo C, Venuti A, Roperto F (2007) Bovine papillomavirus type-2 DNA and expression of E5 and E7 oncoproteins in vascular tumours of the urinary bladder in cattle. Cancer Lett 250:82–89Google Scholar
  15. Bos JL (1989) Ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689Google Scholar
  16. Brandt S, Haralambus R, Schoster A, Kirnbauer R, Stanek C (2008) Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines. J Gen Virol 89:1390–1395Google Scholar
  17. Bringuier PP, Piaton E, Berger N, Debruyne F, Perrin P, Schalken J, Devonec M (1995) Bracken fern-induced bladder tumors in guinea pigs—a model for human neoplasia. Am J Pathol 147:858–868Google Scholar
  18. Brown K, Buchmann A, Balmain A (1990) Carcinogen induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. Proc Natl Acad Sci U S A 87:538–542Google Scholar
  19. Brun R, Urraro C, Medaglia C, Russo V, Borzacchiello G et al (2008) Lymphoepithelioma-like carcinoma of the urinary bladder in a cow associated with bovine papillomavirus type-2. J Comp Pathol 139:121–125Google Scholar
  20. Bryant PE, Gray LJ, Peresse N (2004) Progress towards understanding the nature of chromatid breakage. Cytogenet Genome Res 104:65–71Google Scholar
  21. Campo MS (1997) Bovine papillomavirus and cancer. Vet J 154:175–188Google Scholar
  22. Campo MS (2006) Bovine papillomavirus: old system, new lessons? In: Campo MS (ed) Papillomavirus research from natural history to vaccines and beyond. Caister Academic Press, Norfolk, pp 373–383Google Scholar
  23. Campo MS, McCafferty RE, Doherty I, Kennedy IM, Jarrett WFH (1990) The Harvey ras 1 gene is activated in papillomavirus-associated carcinomas of the upper alimentary canal in cattle. Oncogene 5:303–308Google Scholar
  24. Campo MS, Jarrett WFH, Barron R, O’Neill BW, Smith KT (1992) Association of bovine papillomavirus type 2 and bracken fern with bladder cancer in cattle. Cancer Res 52:6898–6904Google Scholar
  25. Campos-da-Paz M, Pereira LO, Bicalho LS, Dorea JG, Pocas-Fonseca MJ, Almeida Santos MFM (2008) Interaction of bracken-fern extract with vitamin C in human submandibular gland and oral epithelium cell lines. Mutat Res 652:158–163Google Scholar
  26. Carvalho T, Pinto C, Peleteiro MC (2006) Urinary bladder lesions in bovine enzootic haematuria. J Comp Pathol 134:336–346Google Scholar
  27. Carvalho T, Naydan D, Nunes T, Pinto C, Peleteiro MC (2009) Immunohistochemical evaluation of vascular urinary bladder tumors from cows with enzootic hematuria. Vet Pathol 46:211–221Google Scholar
  28. Castillo UF, Ojika M, Sakagami Y, Wilkins AL, Lauren DR, Alonso-Amelot ME, Smith BL (2000) Isolation and structural determination of three new toxic illudane-type sesquiterpene glucosides and a new protoilludane sesquiterpene glucoside from Pteridium aquilinum var. caudatum. In: Taylor JA, Smith RT (eds) Bracken fern: toxicity, biology and control. Proceedings of the international bracken group conference Manchester. Aberystwyth: International Bracken Group, UK, pp 55–59Google Scholar
  29. Chambers G, Ellsmore VA, O’Brien PM, Reid SW, Love S, Campo MS, Nasir L (2003) Association of bovine papillomavirus with the equine sarcoid. J Gen Virol 84:1055–1062Google Scholar
  30. Costa Rui MG, Oliveira PA, Vilanova M, Bastos MMSM, Lopes CC, Lopes C (2011) Ptaquiloside-induced, B-cell lymphoproliferative and early-stage urothelial lesions in mice. Toxicon 58:543–549Google Scholar
  31. Dalbagni G, Ren ZP, Herr H, Cordon-Cardo C, Reuter V (2001) Genetic alterations in tp53 in recurrent urothelial cancer: a longitudinal study. Clin Cancer Res 7:2797–2801Google Scholar
  32. Dawra RK, Sharma OP (2001) Enzootic bovine haematuria—past, present and future. Vet Bull 71:1–27Google Scholar
  33. Dawra RK, Sharma OP, Krishna L (1989) Are environmental conditions responsible for animal-plant carcinogen interaction? A study relating to enzootic bovine haematuria. Environmentalist 9:277–283Google Scholar
  34. Dawra RK, Sharma OP, Krishna L, Vaid JL (1991) The enzymatic profile of urine and plasma in bovine urinary bladder cancer (enzootic bovine haematuria). Vet Res Commun 15:421–426Google Scholar
  35. Dawra RK, Sharma OP, Somvanshi R (2001) A preliminary study on the carcinogenicity of the common fern Onychium contiguum. Vet Res Commun 25:413–420Google Scholar
  36. Dawra RK, Kurade NP, Sharma OP (2002) Carcinogenicity of the fern Pteridium aquilinum collected from enzootic bovine haematuria-free hilly area in India. Curr Sci 83:1005–1009Google Scholar
  37. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H (2004) Classification of papillomaviruses. Virology 324:17–27Google Scholar
  38. Deshmukh S, Banga HS, Kwatra KS, Singh ND, Gadhave PD, Brar RS (2010) Immunohistochemical study on spontaneous transitional cell carcinoma of urinary bladder in an Indian water buffalo (Bubalus bubalis). Indian J Vet Pathol 34:113–116Google Scholar
  39. Engel P, Brandt KK, Rasmussen LH, Ovesen RG, Sorensen J (2007) Microbial degradation and impact of Bracken toxin ptaquiloside on microbial communities in soil. Chemosphere 67:202–209Google Scholar
  40. Epstein JL, Amin MB, Reuter VR (2004) Bladder biopsy interpretation. Lippincott Williams & Wilkins, Philadelphia, PA, pp 11–34Google Scholar
  41. Farajzadeh H, Tehrani AA, Amirarfaei Y, Pourata A, Mansoub NH, Khalili Y, Mohammadi M (2011) Pathological studies on the incidence of bracken-fern induced encephalomalacia in rat. Ann Biol Res 2:386–392Google Scholar
  42. Fenwick GR (1988) Bracken (Pteridium aquilinum)—toxic effects and toxic constituents. J Sci Food Agric 46:147Google Scholar
  43. Fletcher MT, Brock IJ, Reichmann KG, McKenzie RA, Blaney BJ (2011) Norsesquiterpene glycosides in bracken ferns (Pteridium esculentum and Pteridium aquilinum subsp. wightianum) from Eastern Australia: reassessed poisoning risk to animals. J Agric Food Chem 59:5133–5138Google Scholar
  44. Freitas RN, O’Connor PJ, Prakash AS, Shahin M, Povey AC (2001) Bracken (Pteridium aquilinum)-induced DNA adducts in mouse tissues are different from the adduct induced by the activated form of the bracken carcinogen ptaquiloside. Biochem Biophys Res Commun 281:589–594Google Scholar
  45. Freitas RN, Brasileiro-Filho G, Silva ME, Pena SDJ (2002) Bracken fern-induced malignant tumors in rats: absence of mutations in p53, H-ras and K-ras and no microsatellite instability. Mutat Res 499:189–196Google Scholar
  46. Gangwar NK (2004) Studies on pathological effects of linguda (Diplazium esculentum, Retz.) in laboratory rats and guinea pigs. M.V.Sc. Thesis, IVRI Deemed University, Izatnagar-243122, Bareilly, IndiaGoogle Scholar
  47. Gerenutti M, Spinosa HS, Bernardi MM (1992) Effects of bracken fern (Pteridium aquilinum L Kuhn) feeding during the development of female rats and their offspring. Vet Human Toxicol 34:307–310Google Scholar
  48. Giurgiu G, Mircean M, Scurtu I, Popovici C (2008) Epidemiological, clinical and paraclinical investigations in cattle enzootic haematuria in an area from N-W of Transilvania. Bull Univ Agric Sci Vet Med 65:12–15Google Scholar
  49. Gounalan S, Somvanshi R, Kataraia M, Bisht GS, Smith BL, Lauren DR (1999) Effect of bracken (Pteridium aquilinum) and dryopteris (Dryopteris juxtaposita) fern toxicity in laboratory rabbits. Indian J Exp Biol 37:980–985Google Scholar
  50. Hainaut P, Hollstein M (2000) p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 77:81–137Google Scholar
  51. Hartmann A, Schlake G, Zaak D, Hungerhuber E, Hofstetter A, Hofstaedter F, Knuechel R (2002) Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res 62:809–818Google Scholar
  52. Hirayama T (1979) Diet and cancer. Nutr Cancer 1:67–81Google Scholar
  53. Hirono C, Shibuya M, Shizmu K, Fushmi K (1972) Carcinogenic activity of processed bracken as human food. J Natl Cancer Inst 48:1245–1250Google Scholar
  54. Hoffmann JS, Fry M, Williams J, Loeb LA (1993) Codon 12 and 13 of H-ras protooncogene interrupt the progression of DNA synthesis catalyzed by DNA polymerase alpha. Cancer Res 53:2895–2900Google Scholar
  55. Hopkins NCG (1986) Aetiology of enzootic haematuria. Vet Rec 118:715–717Google Scholar
  56. Hopkins NC (1987) Enzootic haematuria in Nepal. Trop Anim Health Prod 19:159–164Google Scholar
  57. Hoque M, Somvanshi R, Singh GR, Mogha IV (2002) Ultrasonographic evaluation of urinary bladder in normal, fern fed and enzootic bovine haematuria-affected cattle. J Vet Med A 49:403–407Google Scholar
  58. Jensen PH, Jacobsen OS, Hansen HC, Juhler RK (2008) Quantification of ptaquiloside and pterosin B in soil and groundwater using liquid chromatography-tandem mass spectrometry (LC-MS/MS). J Agric Food Chem 56:9848–9854Google Scholar
  59. Jones TC, Hunt RO (1983) Veterinary pathology, 5th edn. K. M. Varghese Co., Bombay, pp 1500–1501Google Scholar
  60. Jones PA, Buckley JD, Henderson BE, Ross RK, Pike MC (1991) From gene to carcinogen: a rapidly evolving field in molecular epidemiology. Cancer Res 51:3617–3620Google Scholar
  61. Kerrigan J (1926) Chronic haematuria affecting cattle. Note on cases in the South Island west coast district. N Z J Agric 33:85–87Google Scholar
  62. Krengel U, Schlichting I, Schere A, Schuman R, Frech M, John U, Kabish W, Pai E, Wittinghoffer A (1990) Three dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell 62:539–548Google Scholar
  63. Krontridis TG, Devlin B, Karp DD, Robert NJ, Rish N (1993) An association between the risk of cancer and mutations in the HRAS1 minisatellite locus. N Engl J Med 329:517–523Google Scholar
  64. Kumar AK, Kataria M, Somvanshi R, Kumar S, Saini M (2001) Characterization of toxin from Cheilanthes fern and its effect on lymphocyte proliferation and DNA fragmentation. Indian J Exp Biol 39:1065–1067Google Scholar
  65. Kushida T, Uesugi M, Sugiura Y, Kigoshi H, Tanaka H, Hirokawa J, Ojika M, Yamada K (1994) DNA damage by ptaquiloside, a potent bracken carcinogen: detection of selective strand breaks and identification of DNA cleavage products. J Am Chem Soc 116:479–486Google Scholar
  66. Latorre AO, Caniceiro BD, Wysocki HL Jr, Haraguchi M, Gardner DR, Gorniak SL (2011) Selenium reverses Pteridium aquilinum-induced immunotoxic effects. Food Chem Toxicol 49:464–470Google Scholar
  67. Leishangthem GD (2006) Etio-pathological studies on bovine papillomatosis with special reference to its combined effects on fern fed hamsters. M.V.Sc. Thesis, Deemed University, IVRI, Izatnagar-243 122Google Scholar
  68. Leishangthem GD, Somvanshi R, Tiwari AK (2008) Detection of bovine papillomaviruses in cutaneous warts/papillomas in cattle. Indian J Vet Pathol 32:15–20Google Scholar
  69. Lioi MB, Barbieri R, Borzacchiello G, Dezzi S, Roperto S, Santoro A, Russo V, Roperto F (2004) Chromosome aberration in cattle with chronic enzootic haematuria. J Comp Pathol 113:233–236Google Scholar
  70. Liu R, Xu Y, Chang J (2005) The expression and significance of KA 1 and ki-67 in bladder transitional cell carcinoma. Chin Clin Oncol 2:888–893Google Scholar
  71. Lopez-Beltran A, Montironi R (2004) Non-invasive urothelial neoplasms: according to the most recent WHO classification. Eur Urol 46:170–176Google Scholar
  72. Lu ML, Wikman F, Orntoft TF, Charytonowicz E, Rabbani F, Zhang Z (2002) Impact of alterations affecting the p53 pathway in bladder cancer on clinical outcome, assessed by conventional and array based methods. Clin Cancer Res 8:171–179Google Scholar
  73. Lucena RB, Rissi DR, Kommers GD, Pierezan F, Oliveira-Filho JC, Macedo JTSA, Flores MM, Barros CSL (2011) A retrospective study of 586 tumours in Brazilian cattle. J Comp Pathol 145:20–24Google Scholar
  74. Marliere CA, Wathern P, Freitas SN, Castro MCFM, Galvao MAM (2000) Bracken fern (Pteridium aquilinum) consumption and oesophageal and stomach cancer in the Ouro Preto region, Minas Gerais, Brazil. In: Taylor JA, Smith RT (eds) Bracken fern, toxicity, biology and control. International Bracken Group Special Publication No 4, Manchester, UK, p 144Google Scholar
  75. Marliere CA, Wathern P, Castro MCFM, O’Connor P, Galvao MA (2002) Bracken fern (Pteridium aquilinum) ingestion and oesophageal and stomach cancer. IARC Sci Publ 156:379–380Google Scholar
  76. Marrero E, Bulnes C, Sanchez LM, Palenzuela I, Stuart R, Jacobs F, Romero G (2001) Pteridium aquilinum (bracken fern) toxicity in cattle in the humid Chaco of Tarija, Bolivia. Vet Human Toxicol 43:156–158Google Scholar
  77. Marrero E, Bulnes C, Sanchez LM, Palenzuela J, Stuart R, Jacobs F, Romero J (2004) Chronic toxicity in cattle due to Pteridium aquilinum (bracken fern) in Tarija Department, Bolivia: an interdisciplinary investigation, Chapter 36. In: Acamovic T, Stewart CS, Pennycott TW (eds) Poisonous plants and related toxins. CABI Publishing, Wallingford, pp 248–252Google Scholar
  78. Masui T, Mann AM, Macatee TL, Okamura T, Garland EM, Fujui H, Pelling JC, Cohen SM (1991) H-ras mutations in rat urinary bladder carcinomas induced by nirofurylthiazolyl formamide and sodium saccharin, sodium ascorbate, and related salts. Cancer Res 51:3471–3475Google Scholar
  79. Matsuoka A, Hirosawa A, Natori S, Iwasaki S, Sofuni T, Ishidate M Jr (1989) Mutagenicity of PT, the carcinogen in bracken, and its related illudane-type sesquiterpenes. II. Chromosomal aberration tests with cultured mammalian cells. Mutat Res 215:179–185Google Scholar
  80. Mori H, Sugie S, Hirono I, Yamada K, Niwa H, Ojika M (1985) Genotoxicity of ptaquiloside, a bracken carcinogen, in the hepatocytes primary culture/DNA-repair test. Mutat Res 143:75–78Google Scholar
  81. Nagarajan N, Kumar P, Punetha N, Jensen DJ, Lauren DR, Somvanshi R (2011) Detection of ptaquiloside in certain ferns of Uttarakhand and Tamil Nadu, India. Proceed Ann Congress Vet Pathologists, India, 182Google Scholar
  82. Niwa H, Ojika M, Wakamatsu K, Yamada K, Hirono I, Matsushita K (1983) Ptaquiloside, a novel norsesquiterpene glucoside from bracken, Pteridium aquilinum var. latiusculum. Tetrahedron Lett 24:4117–4120Google Scholar
  83. Ojika M, Wakamatsu K, Niwa H, Yamasa K (1987) Ptaquiloside, a potent carcinogen isolated from bracken fern Pteridium aquilinum var latiusculum: structure elucidation based on chemical and spectral evidence, and reactions with aminoacids, nucleosides and nucleotides. Tetrahedron 43:5261–5274Google Scholar
  84. Ojika M, Sugimoto K, Okazaki T, Yamada K (1989) Modification and c1eavage of DNA by ptaquiloside. A new potent carcinogen isolated from bracken fern. J Chem Soc Chem Commun 22:1775Google Scholar
  85. Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P (2002) The IARC TP53 database: new online mutation analysis and recommendations to users. Human Mutat 19:607–614Google Scholar
  86. Ovesen RG, Rasmussen LH, Hansen HC (2008) Degradation kinetics of ptaquiloside in soil and soil solution. Environ Toxicol Chem 27:252–259Google Scholar
  87. Pangty K, Singh S, Goswami R, Saikumar G, Somvanshi R (2010a) Detection of BPV-1 and -2 and quantification of BPV-1 by Real time PCR in cutaneous warts in cattle and buffaloes. Transbound Emerg Dis 57:185–196Google Scholar
  88. Pangty K, Singh S, Pandey AB, Somvanshi R (2010b) Preliminary binary ethylenimine inactivated bovine papillomavirus (BPV) vaccine trial against cutaneous warts in bull calves: a pathological assessment. Braz J Vet Pathol 3:105–111Google Scholar
  89. Pathania S, Kumar P, Leishangthem GD, Kumar D, Dhama K, Somvanshi R (2011) Preliminary assessment of binary ethylenimine inactivated and saponized cutaneous warts (BPV-2) therapeutic vaccine for enzootic bovine haematuria in hill cows. Vaccine 29(43):7296–7302. doi: 10.1016/j.vaccine.2011.07.065 Google Scholar
  90. Pathania S, Dhama K, Saikumar G, Shahi S, Somvanshi R (2012) Detection and quantification of bovine papilloma virus type 2 (BPV-2) by real-time PCR in urine and urinary bladder lesions in enzootic bovine haematuria (EBH)-affected cows. Transbound Emerg Dis 59:79–84Google Scholar
  91. Pennie WD, Campo MS (1992) Synergism between BPV-4 and the flavonoid quercetin in cell transformation in vitro. Virology 190:861–865Google Scholar
  92. Peretti V, Ciotola F, Albarella S, Russo V, Di Meo GP, Lannuzzi L, Roperto F, Barbieri V (2007) Chromosome fragility in cattle with chronic enzootic haematuria. Mutagenesis 22:317–320Google Scholar
  93. Perez-Alenza MD, Blanco J, Sardon D, Sanchez Moreiro MA, Rodriguez-Bertos A (2006) Clinico-pathological findings in cattle exposed to chronic bracken fern toxicity. N Z Vet J 54:185–192Google Scholar
  94. Pinto C, Januario T, Geraldes M, Machado J, Lauren DR, Smith BL, Robinson RC (2004) Bovine enzootic haematuria on São Miguel Island, Chapter 84. In: Acamovic T, Stewart CS, Pennycott TW (eds) Poisonous plants and related toxins. CABI Publishing, Wallingford, UK, pp 564–574Google Scholar
  95. Prakash AS, Pereira TN, Smith BL, Shaw G, Seawright AA (1996) Mechanism of bracken fern carcinogenesis: evidence for H-ras activation via initial adenine alkylation by ptaquiloside. Nat Toxins 4:221–227Google Scholar
  96. Prescott JL, Montie J, Pugh TW, McHugh T, Veltri RW (2001) Clinical sensitivity of p53 mutation detection in matched bladder tumour, bladder wash, and voided urine specimens. Cancer 91:2127–2135Google Scholar
  97. Przybojewska B, Jagiello A, Jalmuzna P (2000) H-RAS, K-RAS, and N-RAS gene activation in human bladder cancers. Cancer Genet Cytogenet 121:73–77Google Scholar
  98. Rai GK, Saxena M, Singh V, Somvanshi R, Sharma B (2011) Identification of bovine papilloma virus 10 in teat warts of cattle by DNase-SISPA. Vet Microbiol 147:416–419Google Scholar
  99. Rajasekaran D, Somvanshi R (2001) Evaluation of pathological effects of Cheilanthes farinosa, Onychium contiguum ferns and their combined effect in rats. J Lab Med 2:33–40Google Scholar
  100. Rajasekaran D, Somvanshi R, Dawra RK (2004) Clinical and haematological studies on Cheilanthes farinosa, Onychium contiguum and their combined effects in laboratory rats. Indian J Anim Sci 74:11–14Google Scholar
  101. Rasmussen LH (2003) Occurrence and fate of a Bracken (Pteridium sp.) toxin in terrestrial environments. Ph.D. Thesis, Chemistry Department, The Royal Veterinary and Agricultural University DK-1871 Frederiksberg C, DenmarkGoogle Scholar
  102. Rasmussen LH, Hansen HCB (2003) Growth of Bracken in 953 Denmark and the content of ptaquiloside in fronds, 954 rhizomes and roots. In: Acamovic T, Stewart CS, Pennycott TW (eds) Poisonous plants and related 956 toxins. CAB International, Wallingford, UK, p 955Google Scholar
  103. Rasmussen LH, Jensen LS, Hansen HCB (2003a) Distribution of the carcinogenic terpene ptaquiloside in bracken fronds, rhizomes (Pteridium aquilinum), and litter in Denmark. J Chem Ecol 29:771–778Google Scholar
  104. Rasmussen LH, Kroghsbo S, Frisvad JC, Hansen HCB (2003b) Occurrence of the carcinogenic bracken constituent ptaquiloside in fronds, topsoils and organic soil layers in Denmark. Chemosphere 51:117–127Google Scholar
  105. Rasmussen LH, Hansen HCB, Lauren DR (2005) Sorption, degradation, and mobility of ptaquiloside, a carcinogenic bracken (Pteridium sp.) constituent, in the soil environment. Chemosphere 58:823–835Google Scholar
  106. Rasmussen LH, Lauren DR, Smith BL, Hansen HCB (2008) Variation in ptaquiloside content in bracken (Pteridium esculentum (Forst. f) Cockayne) in New Zealand. N Z Vet J 56:304–309Google Scholar
  107. Ravisankar R (2004) Studies on long term pathological effects of bracken fern (Pteridium aquilinum) in laboratory rats and hill cattle. Ph.D. Thesis, Deemed University, Indian Veterinary Research Institute, Izatnagar-243 122 (UP), IndiaGoogle Scholar
  108. Ravisankar R, Somvanshi R, Tandon SK, Naik A (2005) Behavioural and pathological studies on laboratory rats fed with crude extract of bracken fern. Toxicol Int 12:125–128Google Scholar
  109. Reddy MV, Randerath K (1987) 32P-postlabeling assay for carcinogen-DNA adducts: nuclease P1-mediated enhancement of its sensitivity and applications. Environ Health Perspect 76:41Google Scholar
  110. Resendes AR, Roperto S, Trapani F, Urraro C, Rodrigues A, Roperto F, Borzacchiello G (2011) Association of BPV-2 and urinary bladder tumours in cattle from the Azores archipelago. Res Vet Sci 90:526–529Google Scholar
  111. Roperto S, Roberto B, Paolini F, Urraro C, Russo V, Borzacchiello G, Pagnini U, Raso C, Rizzo C, Roperto F, Venuti A (2008) Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role. J Gen Virol 89:3027–3033Google Scholar
  112. Roperto S, Borzacchiallo G, Brun R, Leonardi L, Maiolino P, Martano M, Paciello O, Papparella S, Restucci B, Russo V, Salvatore G, Urraro C, Roperto F (2010) A review of bovine urothelial tumours and tumour-like lesions of the urinary bladder. J Comp Pathol 142:95–108Google Scholar
  113. Saito K, Nagao T, Matoba M, Koyama K, Natori S, Murakami T, Saiki Y (1989) Chemical assay of ptaquiloside, the carcinogen of Pteridium aquilinum, and the distribution of related compounds in the pteridaceae. Phytochemistry 28:1605–1611Google Scholar
  114. Saito K, Nagao T, Takatsuki S, Koyama K, Natori S (1990) The sesquiterpenoid carcinogen of bracken fern and some analogues, from the pteridaceae. Phytochemistry 29:1475–1479Google Scholar
  115. Santos RC, Brasileiro-Filho G, Hojo ES (1987) Induction of tumors in rats by bracken fern (Pteridium aquilinum) from Ouro Preto (Minas Gerais, Brazil). Braz J Med Biol Res 20:73–77Google Scholar
  116. Santos RC, Brasileiro-Filho G, Silva ME (1992) Tumorigenicity of boiling water extract of bracken fern (P. aquilinum (L.) Kuhn). Ciência e Tecnologia de Alimentos 12:72–76Google Scholar
  117. Santos RCS, Lindsey CJ, Ferraz OP, Pinto JR, Mirandola RS, Benesi FJ, Birgel EH, Pereira CAB, Becak W (1998) Bovine Papillomavirus transmission and chromosomal aberrations: on experimental model. J Gen Virol 79:2127–2135Google Scholar
  118. Sardon D, de la Fuente I, Calonge E, Perez-Alenza MD, Castano M, Dunner S, Pena L (2005) H-ras immunohistochemical expression and molecular analysis of urinary bladder lesions in grazing adult cattle exposed to bracken fern. J Comp Pathol 132:195–201Google Scholar
  119. Schmidt B, Rasmussen LH, Svendsen GW, Ingerslev F, Hansen HCB (2005) Genotoxic activity and inhibition of soil respiration by ptaquiloside, a bracken fern carcinogen. Environ Toxicol Chem 24:2751–2756Google Scholar
  120. Shahin M, Moore MR, Worrall S, Smith BL, Seawright AA, Prakash AS (1998a) H-ras activation is an early event in the ptaquiloside induced carcinogenesis: comparison of acute and chronic toxicity in rats. Biochem Biophys Res Commun 250:491–497Google Scholar
  121. Shahin M, Smith BL, Worral S, Moore MR, Seawright AA, Prakash AS (1998b) Bracken fern carcinogenesis: multiple intravenous doses of activated ptaquiloside induce DNA adducts, monocytosis, increased TNFa levels and mammary gland carcinoma in rats. Biochem Biophys Res Commun 244:192–197Google Scholar
  122. Shahin M, Smith BL, Prakash AS (1999) Bracken carcinogens in the human diet. Mutat Res 443:69Google Scholar
  123. Shigyo M, Sugano K, Tobisu K, Tsukamoto T, Sekiya T, Kakizoe T (2001) Molecular follow up of newly diagnosed bladder cancer using urine samples. J Urol 166:1280–1285Google Scholar
  124. Siman SE, Povey AC, Ward TH, Margison GP, Sheffield E (2000) Fern spore extracts can damage DNA. Br J Cancer 83:69–73Google Scholar
  125. Singh V (2007) Etio-pathological studies on bovine papillomatosis and enzootic bovine haematuria with special reference to combined effects of BPV and fern in hamsters. M.V.Sc. Thesis submitted to Deemed University, IVRI, Izatnagar-243 122, UP, IndiaGoogle Scholar
  126. Sivasankar S, Somvanshi R (2001) Pathological evaluation of Polystichum squarrosum (D. Don) fern in laboratory rats Indian. J Exp Biol 39:772–776Google Scholar
  127. Smith BL, Beatson NS (1970) Bovine enzootic haematuria in New Zealand. N Z Vet J 18:115–120Google Scholar
  128. Smith BL, Embling PP, Agnew MP, Lauren DR, Holland PT (1988) Carcinogenicity of bracken fern (Pteridium esculentum) in New Zealand. N Z Vet J 36:56–58Google Scholar
  129. Smith BL, Embling PP, Lauren DR, Agnew MP, Ross AD, Greentree PL (1989) Carcinogen in rock fern (Chelianthus sieberi) from New Zealand and Australia. Aust Vet J 66:154–155Google Scholar
  130. Smith BL, Embling PP, Lauren DR, Agnew MP (1992) Carcinogenicity of Pteridium esculentum and Cheilanthes sieberi in Australia and New Zealand. In: James LF, Keeler RF, Bailey EM, Cheeke PR, Hegarty MP (eds) Poisonous plants. Proceedings of the third international symposium. Iowa State University Press, Ames, IA, p 448Google Scholar
  131. Smith BL, Seawright AA, Ng JC, Hertle AT, Tomson JA, Bostock PD (1994a) Concentration of ptaquiloside, a major carcinogen in bracken fern (Pteridium spp.), from eastern Australia and from a cultivated worldwide collection held in Sydney, Australia. Nat Toxins 2:347–353Google Scholar
  132. Smith BL, Seawright AA, Ng JC, Hertle AT, Thomson JA, Bostock PD (1994b) Concentration of ptaquiloside, a major carcinogen in bracken fern (Pteridium spp.), from Eastern Australia and from a cultivated worldwide collection held in Sydney, Australia. Nat Toxins 2:347–353Google Scholar
  133. Smith BL, Shaw G, Prakash AS, Seawright AA (1994c) Studies on DNA formation by ptaquiloside, the carcinogen of bracken ferns Pteridium spp. In: Colegate SM, Dorling PR (eds) Plant associated toxins: agricultural, phytochemical and ecological aspects. CAB International, Wallingford, UK, pp 167–172Google Scholar
  134. Smith ND, Rubenstein JN, Eggener SE, Kozlowski JM (2003) The p53 tumour suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol 169:1219–1228Google Scholar
  135. Somvanshi R, Lauren DR, Smith BL, Dawra RK, Sharma OP, Sharma VK, Singh AK, Gangwar NK (2006) Estimation of the fern toxin, ptaquiloside, in certain Indian ferns other than bracken. Curr Sci 91:1547–1552Google Scholar
  136. Sood S, Dawra RK, Sharma OP, Kurade NP (2003) Exposure to the fern Onychium contiguum causes increase in lipid peroxidation and alters antioxidant status in urinary bladder. Biochem Biophys Res Commun 302:476–479Google Scholar
  137. Ushijima J, Matsukawa K, Yuasa A et al (1983) Toxicities of bracken fern in guinea pigs. Jpn J Vet Sci 45:593–603Google Scholar
  138. van der Hoeven JCM, Lagerweij WJ, Posthumus MA, Veldhuizen A, Holterman HAJ (1983) Aquilide A, a new mutagenic compound isolated from bracken fern (P. aquilinum (L.) Kuhn). Carcinogenesis 4:1587–1590Google Scholar
  139. Villalobos-Salazar L, Hernandez H, Meneses A, Salazar G (1999) Bracken fern: toxicity, biology and control. In: Taylor JA, Smith RT (eds) Proceedings of the International Bracken Group, 4th International Bracken Conference, University of Manchester, pp 68–75Google Scholar
  140. Wosiacki SR, Barreiro MAB, Alfieri AF, Alfieri AA (2005) Semi-nested PCR for detection and typing of bovine Papillomavirus type 2 in urinary bladder and whole blood from cattle with enzootic haematuria. J Virol Methods 126:215–219Google Scholar
  141. Wosiacki SR, Claus MP, Alfieri AF, Alfieri AA (2006) Bovine papillomavirus type 2 detection in the urinary bladder of cattle with chronic enzootic haematuria. Mem Inst Oswaldo Cruz, Rio de Janeiro 101:635–638Google Scholar
  142. Yoshida M, Saito T (1994) Acute toxicity of braxin C, a bracken toxin, in guinea pigs. J Toxicol Sci 19:17–23Google Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Disease Investigation LaboratoryIndian Veterinary Research Institute, Regional StationPalampurIndia
  2. 2.Indian Veterinary Research Institute, Regional StationPalampurIndia

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