Skip to main content

The Mycotoxin Fumonisin Induces Apoptosis in Cultured Human Cells and in Livers and Kidneys of Rats

  • Chapter
Fumonisins in Food

Abstract

Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme, a fungus that infects corn and other grains in the U.S. Fumonisin ingestion causes a variety of effects including equine leukoencephalomalacia and porcine pulmonary edema, and has been associated epidemiologically with human esophageal cancer. Fumonisin B1 produces growth inhibition and increased apoptosis in primary human keratinocyte cultures and in HET-1A cells. In order to set the doses for a 2-year tumor bioassay, male and female F344 rats were fed fumonisin B1 (99, 163, 234, and 484 ppm) for 28 days and the organs examined histologically. There was a dose dependent decrease in liver and kidney weights in the rats. The liver weight loss was accompanied by the induction of apoptosis and hepatocellular and bile duct hyperplasia in both sexes, with the female rats being more responsive at lower doses. The induction of tubular epithelial cell apoptosis was the primary response of the kidneys to dietary fumonisin B1. Apoptosis was present at all doses in the kidneys of the male rats, and occurred in the females only at 163, 234, and 484 ppm fumonisin B1. These results demonstrate that fumonisin B1 treatment causes a similar increase in apoptosis both in vivo and in vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bendetti, A.; Jézéquel, A.M.; Orlandi, F. Preferential distribution of apoptotic bodies in acinar zone 3 of the normal human and rat liver. J. Hepatol 1988, 7, 319–324.

    Article  Google Scholar 

  • Bezuidenhout, S.C.; Gelderblom, W.C.A.; Gorst-Allman, C.P.; Horak, R.M.; Marasas, W.F.O.; Spiteller, G.; Vleggaar, R. Structure elucidation of the fumonisins, mycotoxins from Fusarium moniliforme. J. Chem. Soc. Chem. Commun., 1988, 743-745.

    Google Scholar 

  • Binder, C.; Hiddemann, W. Programmed cell death-many questions still to be answered. Ann. Hematol 1994, 69, 45–55.

    Article  CAS  Google Scholar 

  • Cawood, M.E.; Gelderblom, W.C.A.; Vleggaar, R.; Behrend, Y.; Thiel, P.G.; Marasas, W.F.O. Isolation of the fumonisin mycotoxins: A quantitative approach. J. Agric. Food Chem., 1991, 39, 1958–1962.

    Article  CAS  Google Scholar 

  • Dombrink-Kurtzman, M.A.; Bennett, G.A.; Richard, J.L. An optimized MTT bioassay for determination of cytotoxicity of fumonisins in turkey lymphocytes. J. A.O.A.C. International, 1994, 77, 512–516.

    CAS  Google Scholar 

  • Flemming, W. Uber die bildung von richtungsfiguren in säugethiereiern beim untergang graafscher follikel. Arch. Anat. Entwgesch., 1885, 221-224.

    Google Scholar 

  • Gelderblom, W.C.A.; Marasas, W.F.O.; Vleggaar, R.; Thiel, P.G.; Cawood, M.E. Fumonisins: Isolation, chemical characterization and biological effects. Mycopatholia, 1992a, 117, 11–16.

    Article  CAS  Google Scholar 

  • Gelderblom, W.C.A.; Semple, E.; Marasas, W.F.O.; Farber, E. The cancer-initiating potential of the fumonisin B mycotoxins. Carcinogenesis, 1992b, 13, 433–437.

    Article  CAS  Google Scholar 

  • Hannun, Y.A.; Loomis, C.R.; Merrill, Jr., A.H.; Bell, R.M. Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. J. Biol. Chem., 1986, 261, 12604–12609.

    CAS  Google Scholar 

  • Holcomb, M.; Sutherland, J.B.; Chiarelli, M.P.; Korfmacher, W.A.; Thompson, Jr., H.C.; Lay, Jr., J.O.; Hankins, L.J.; Cerniglia, C.E. HPLC and FAB mass spectrometry analysis of fumonisins B1 and B2 produced by Fusarium moniliforme on food substances. J. Agric. Food Chem., 1993a, 41, 357–360.

    Article  CAS  Google Scholar 

  • Holcomb, M.; Thompson, Jr., H.C.; Hankins, L.J. Analysis of fumonisin B1 in rodent feed by gradient elution PLC using precolumn derivatization with FMOC and fluorescence detection. J. Agric. Food Chem., 1993b, 41, 764–767.

    Article  CAS  Google Scholar 

  • Huntsberger, D.V.; Billingsley, P. Elements of statistical inference, fourth edition; Allyn and Bacon, Inc.: Boston, MA, 1977.

    Google Scholar 

  • Iype, P.T.; Gabriel, B.W.; Stoner, G.D.; Kaighn, M.E. A serum-free medium for human epidermal-like cells. In Vitro Dev. Biol., 1993, 29A, 94–96.

    Article  CAS  Google Scholar 

  • Jones, C.; Huang, H.; Dickman, M.; Henderson, G.; Wang, H.; Gilchrist, D. Analysis of a carcinogen, fumonisin, which is a fungal toxin. Proc. Amer. Assoc. Cancer Res., 1995, 36, 668.

    Google Scholar 

  • Kane, A.B. Redefining cell death. Amer. J. Pathol., 1995, 146, 1–18.

    CAS  Google Scholar 

  • Kerr, J.F.R. Shrinkage necrosis: a distinct mode of cellular death. J. Pathol., 1971, 105, 13–20.

    Article  CAS  Google Scholar 

  • Kerr, J.F.R.; Harmon, B.; Searle, J. An electron-microscope study of cell deletion in the anuran tadpole tail during spontaneous metamorphosis with special reference to apoptosis of striated muscle fibres. J. Cell Science, 1974, 14, 571–585.

    CAS  Google Scholar 

  • Kerr, J.F.R.; Searle, J.; Harmon, B.V.; Bishop, C.J. Apoptosis, IN Perspectives on Mammalian Cell Death, Potten, C.S., Ed; Oxford University Press: Oxford, 1987.

    Google Scholar 

  • Korsmeyer, S.J. Regulation of cell death. Trends in Genetics, 1995, 11, 101–105.

    Article  CAS  Google Scholar 

  • Merrill, Jr., A.H.; Jones, D.D. An update of the enzymology and regulation of sphingomyelin metabolism. Biochim. Biophys. Acta, 1990, 1044, 1–12.

    Article  CAS  Google Scholar 

  • National Toxicology Program. Specifications for the Conduct of Studies to Evaluate the Toxic and Carcinogenic Potential of Chemical, Biological and Physical Agents in Laboratory Animals for the National Toxicology Program: National Toxicology Program, 1991.

    Google Scholar 

  • Nelson, P.E.; Plattner, R.D.; Shackelford, D.D.; Desjardins, A.E. Production of fumonisins by Fusarium moniliforme strains from various substrates and geographic areas. Appl. Environ. Microbiol. 1991, 57, 2410–2412.

    CAS  Google Scholar 

  • Pirisi, L.; Yasumoto, S.; Feller, M; Doniger, J.; DiPaolo, J.A. Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. J. Virology, 1987, 61, 1061–1066.

    CAS  Google Scholar 

  • Polakowska, R.R.; Haake, A.R. Apoptosis: the skin from a new perspective. Cell Death and Differentiation, 1994, 7, 19–31.

    Google Scholar 

  • Ross, P.F.; Rice, L.G.; Osweiler, G.D.; Nelson, P.E.; Richard, J.L.; Wilson, T.M. A review and update of animal toxicoses associated with fumonisin-contaminated feeds and production of fumonisins by Fusarium isolates. Mycopathologia, 1992, 117, 109–114.

    Article  CAS  Google Scholar 

  • Stevens, V.L.; Nimkar, S.; Jamison, W.C.L.; Liotta, D.C.; Merrill, Jr., A.H. Characteristics of the growth inhibition and cytotoxicity of long-chain (sphingoid) bases for Chinese hamster ovary cells: Evidence for an involvement of protein kinase C. Biochim. Biophys. Acta, 1990, 1051, 37–45.

    Article  CAS  Google Scholar 

  • Stoner, G.D.; Kaighn, M.E.; Reddel, R.R.; Resau, J.H.; Bowman, D.; Naito, Z.; Matsukura, N.; You, M.; Galati, A.J.; Harris, C.C. Establishment and characterization of SV40 T-antigen immortalized human esophageal epithelial cells. Cancer Res., 1991, 51, 365–371.

    CAS  Google Scholar 

  • Thiel, P.G.; Marasas, W.F.O.; Sydenham, E.W.; Shephard, G.S.; Gelderblom, W.C.A.; Nieuwenhuis, J.J. Survey of fumonisin production by Fusarium species. Applied and Environmental Microbiology, 1991, 57, 1089–1093.

    CAS  Google Scholar 

  • Tolleson, W.H.; Melchior, W.B., Jr,; Morris, S.M.; McGarrity, L.J.; Domon, O.E.; Muskhelishvili, L.; James, S.J.; Howard, P.C. Apoptosis and antiproliferative effects of fumonisin B1 in human keratinocytes, fibroblasts, esophageal epithelial cells, and hepatoma cells. Carcinogenesis, in press.

    Google Scholar 

  • Toxicological Principals for the Safety Assessment of Direct Food Additives and Color Additives Used in Foods, “Redbook II”. United States Food and Drug Administration, Center for Food Safety and Applied Nutrition, 1993.

    Google Scholar 

  • Voss, K.A.; Chamberlain, W.J.; Bacon, C.W.; Norred, W.P. A preliminary investigation on renal and hepatic toxicity in rats fed purified fumonisin B1. Natural Toxins, 1993, 1, 222–228.

    Article  CAS  Google Scholar 

  • Voss, K.A.; Chamberlain, W.J.; Bacon, C.W.; Herbert, R.A.; Walters, D.B.; Norred, W.P. Subchronic feeding study of the mycotoxin fumonisin Bl in B6C3F1 mice and Fischer 344 rats. Fund. Appl. Toxicol., 1995, 24, 102–110.

    Article  CAS  Google Scholar 

  • Wang, E.; Norred, W.P.; Bacon, C.W.; Riley, R.T.; Merrill, Jr., A.H. Inhibition R J. Biological Chemistry, 1991, 266, 14486–14490.

    CAS  Google Scholar 

  • Wyllie, A.H. Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview. Cancer and Metastasis Reviews, 1992, 11, 95–103.

    Article  CAS  Google Scholar 

  • Wyllie, A.H.; Morris, R.G. Hormone-induced cell death: purification and properties of thymocytes undergoing apoptosis after glucocorticoid treatment. Am. J. Pathol., 1982, 109, 78–87.

    CAS  Google Scholar 

  • Yoo, H.-S.; Showker, J.L.; Riley, R.T. Relationship between fumonisin (FB)-induced cytotoxicity and the elevation of free sphinganine (Sa) in LLC-PK1 cells. The Toxicologist, 1994, 14, 772.

    Google Scholar 

  • Yoo, H.-S.; Showker, J.L.; Riley, R.T. Partitioning of increased sphinganine (Sa) and decreased complex sphingolipids (CSL) as causative factors in fumonisin B1 (FB1)-induced cytostatic and cytotoxic effects in LLC-PK1 cells. The Toxicologist, 1995, 15, 1555.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paul C. Howard .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

Tolleson, W.H., Dooley, K.L., Sheldon, W.G., Thurman, J.D., Bucci, T.J., Howard, P.C. (1996). The Mycotoxin Fumonisin Induces Apoptosis in Cultured Human Cells and in Livers and Kidneys of Rats. In: Jackson, L.S., DeVries, J.W., Bullerman, L.B. (eds) Fumonisins in Food. Advances in Experimental medicine and Biology, vol 392. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1379-1_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-1379-1_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1381-4

  • Online ISBN: 978-1-4899-1379-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics