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5-Fluorouracil Accumulation in Green Microalgae and its Biogenetic Transfer into Ciliate Protozoan


The study has demonstrated that anticancer drug 5-fluorouracil causes acute toxicity and interferes with the growth of green microalgae, Scenedesmus vacuolatus. It accumulates in microalgae biomass with bioaccumulation factor of 1.84 × 104 and further integrates into the DNA and RNA of microalgae. In addition, the labelled microalgae genome is transferred into protozoan Tetrahymena pyriformis on feeding and is retained in the food vacuoles of predator organisms. This biotransfer of labelled 5-fluorouracil via genomic material was evaluated using radioactivity in Tetrahymena cell pellets though radioactivity did not detect anticancer drug in the genome of the predator organism.

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  1. Arellano M, Malet-Martino M, Martino R, Gires P (1998) The anti-cancer drug 5-fluorouracil is metabolized by the isolated perfused rat liver and in rats into highly toxic fluoroacetate. Brit J Can 77:79–86

    Article  CAS  Google Scholar 

  2. Diasio RB, Harris BE (1989) Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet 16:215–237

    Article  CAS  Google Scholar 

  3. Heberer T, Butz S, Stan H-J (1995) Analysis of phenoxy carboxylic acids and other acidic compounds in tap, ground, surface and sewage water at the low ppt level. Int J Environ Anal Chem 58:43–54

    Article  CAS  Google Scholar 

  4. Ingraham HA, Tseng BY, Goulian M (1982) Nucleotide levels and incorporation of 5-fluorouracil and uracil into DNA of cells treated with fluorodeoxyuridine. Mol Pharmacol 21:211–216

    CAS  Google Scholar 

  5. Kiffmeyer TK, Götze HJ, Jursch M, Lüders U (1998) Trace enrichment, chromatographic separation and biodegradation of cytostatic compounds in surface water. Fresenius Anal Chem 361:185–191

    Article  CAS  Google Scholar 

  6. Klinger J, Brauch HJ (2000) Water quality of the rivers Danube and its tributaries. Poster presented at the annual meeting of the German society of water chemistry, Weimar, Proceedings

  7. Kufe DW, Scott P, Fram R, Major P (1983) Biologic effect of 5-fluoro-2′ deoxyribonucleic acid incorporation deoxyuridine in mammalian cells. Mutat Res 258:161–188

    Google Scholar 

  8. Kümmerer K (1998) Abbau von Arzneimitteln in Testsystemen und Möglichkeiten zur Emissionsreduktion. In: Weigert B, Steinberg Chr, Brüggemann R (eds) Schriftenreihe Wasserforschung 6 Chemische Stressfaktoren in aquatischen Systemen, Berlin

  9. Kümmerer K (2000) Laboratory scale degradation of pharmaceuticals and emission control (Abbau von Arzneimitteln in Testsystemen und Möglichkeiten zur Emissionsreduktion). In: Weigert, B

  10. Kümmerer K (2001) Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sources. Chemosphere 45:957–969

    Article  Google Scholar 

  11. Kümmerer K, Al-Ahmad A (1997) Biodegradability of the anti-tumor agents 5-fluorouracil, cytarabine, and gemcitabine: impact of the chemical structure and synergistic toxicity with hospital effluent. Acta hydrochim et hydrobiol 25:166–172

    Article  Google Scholar 

  12. Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5):330–338

    Article  CAS  Google Scholar 

  13. Mahnik SN, Lenz K, Weissenbacher N, Mader R, Fuerhacker M (2007) Fate of 5-fluorouracil, doxorubicin, epirubicin, and daunorubicin in hospital wastewater and their elimination by activated sludge and treatment in a membrane-bio-reactor system. Chemosphere 66:30–37

    Article  CAS  Google Scholar 

  14. Mayo VS, Andrean BAG, De Kloet SR (1968) Effect of cyclophosphamide and 5-fluorouracil on the synthesis of ribonucleic acid in yeast. Biochem et Biophy Acta 169:297–305

    CAS  Google Scholar 

  15. Morris SM (1993) The genetic toxicology of 5-fluoropyrimidines and 5-chlorouracil. Mut Res 297:39–51

    CAS  Google Scholar 

  16. Omura K (2003) Clinical implications of dihydropyrimidine dehydrogenase (DPD) activity in 5FU-based chemotherapy: mutations in the DPD gene and DPD inhibitory fluoropyrimidines. Int J Clin Oncol 8:132–138

    Article  CAS  Google Scholar 

  17. Rich TA, Shepard RC, Mosley ST (2004) Four decades of continuing innovation with fluorouracil: current and future approaches to fluorouracil chemo-radiation therapy. J Clin Oncol 22:2214–2232

    Article  CAS  Google Scholar 

  18. Schalhorn A, Kuhl M (1992) Clinical pharmacokinetics of fluorouracil and folinic acid. Sem Oncol 19:82–92

    CAS  Google Scholar 

  19. Scheutz JD, Diasio RB (1985) The effect of 5-fluorouracil on DNA chain elongation in intact bone marrow cells. Biochem Biophy Res Commun 133:361–367

    Article  Google Scholar 

  20. Susanne N, Mahnik E, Blanka R, Maria F, Robert MM (2004) Determination of 5-fluorouracil in hospital effluents. Anal Bioanal Chem 380:31–35

    Google Scholar 

  21. Ternes T (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:245–3260

    Article  Google Scholar 

  22. UBAFB (1996) Forschungsbericht des Umweltbundesamtes 102 06 514:95-075

  23. Ud-Daula A, Pfister G, Schramm K-W (2008) Growth inhibition and biodegradation of catecholamines in the ciliated protozoan T. pyriformis. J Environ Sci Health Tox Hazard Subst Environ Eng. 43(14):1610–1617

    Article  CAS  Google Scholar 

  24. Wang Z, Ud-Daula A, Pfister G, Schramm K-W (2009) Impact of fluorotelomer alcohols (FTOH) on the molecular and macroscopic phenotype of Tetrahymena thermophila. J Environ Sci Poll Res Int. doi:10.1007/s11356-009-0135-3

    Google Scholar 

  25. Zuccato E, Bagnatir R, Fioretti F, Natangeleo M, Calamari D, Fanelli R (2001) Environmental loads and detection of pharmaceuticals in Italy. In: K. Kümmerer, Editor, Pharmaceuticals in the environment. sources, fate, effects and risks, Springer, Heidelberg

  26. Zurita JL, Jos A, Cameán AM, Salguero M, López-Artíguez M, Repetto G (2007) Ecotoxicological evaluation of sodium fluoroacetate on aquatic organisms and investigation of the effects on two fish cell lines. Chemosphere 67:1–12

    Article  CAS  Google Scholar 

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This research was supported and funded by Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. The authors want to thank the Institute of Plant Physiology, University of Göttingen, Germany, and Institute of Biology: Ecotoxicology and Biochemistry, Free University of Berlin, Germany, for kindly providing microalgae and protozoan culture.

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Correspondence to Asad Ud-Daula.

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Ud-Daula, A., Pfister, G. & Schramm, KW. 5-Fluorouracil Accumulation in Green Microalgae and its Biogenetic Transfer into Ciliate Protozoan. Bull Environ Contam Toxicol 88, 548–554 (2012).

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  • Bioaccumulation
  • Acute toxicity of 5-fluorouracil
  • Genetic transfer of 5-FU
  • Microalgae