English
French
Discovery and occurrence of the fumonisins: a historical perspective.
Abstract: This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isolated from moldy corn implicated in a field outbreak of equine leukoencephalomalacia (ELEM) in South Africa in 1970 was Fusarium verticillioides (F. moniliforme). This fungus was also prevalent in moldy home-grown corn consumed by people in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa. Culture material on corn of F. verticillioides strain MRC 826, which was isolated from moldy corn in Transkei, was shown to cause ELEM in horses, porcine pulmonary edema (PPE) syndrome in pigs, and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when fumonisins B1 and B2 novel mycotoxins with cancer-promoting activity in rat liver, were isolated from culture material of F. verticillioides MRC 826 at the Programme on Mycotoxins and Experimental Carcinogenesis of the Medical Research Council in Tygerberg, South Africa. Following the elucidation of the chemical structure of the fumonisins, these carcinogenic mycotoxins were shown to occur naturally in moldy corn in Transkei. Shortly thereafter, high levels of fumonisins in the 1989 U.S. corn crop resulted in large-scale field outbreaks of ELEM and PPE in horses and pigs, respectively, in the United States. Subsequently the fumonisins were found to occur naturally in corn worldwide, including corn consumed as the staple diet by people at high risk for EC in Transkei and China. These findings, together with the fact that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism, have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fumonisins in 1988.
Publication Date: 2001-05-22 PubMed ID: 11359691PubMed Central: PMC1240671DOI: 10.1289/ehp.01109s2239Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Historical Article
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research study summarizes and highlights the events leading to the discovery of carcinogenic mycotoxins, known as fumonisins, in South Africa in 1988, and the first decade of related research.
Discovering Fumonisins
- Fumonisins were first discovered in South Africa in 1988 during the investigation of an equine leukoencephalomalacia (ELEM) outbreak in horses, which was traced back to moldy corn infested by Fusarium verticillioides fungus.
- The same fungus was prevalent in moldy home-grown corn consumed in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa.
- A strain of F. verticillioides named MRC 826 was cultured from the moldy corn from Transkei and was found to induce not only ELEM in horses but also porcine pulmonary oedema (PPE) syndrome in pigs and liver cancer in rats.
- The carcinogens causing these diseases were then isolated through a short-term cancer initiation/promotion assay in rat liver.
- The isolation process resulted in the discovery of fumonisin B1 and B2 – novel mycotoxins exhibiting cancer-promoting activity in rat liver.
The Distribution and Impact of Fumonisins
- After the chemical structure of the fumonisins was determined, the presence of these carcinogenic mycotoxins was confirmed in moldy corn in the Transkei region.
- In 1989, high levels of fumonisins were found in the U.S. corn crop, leading to large-scale ELEM and PPE outbreaks in horses and pigs in the U.S.
- Subsequent research found that fumonisins naturally occur in corn worldwide, including in areas with high risk of EC such as Transkei and China, where corn is a staple diet.
- These findings, combined with the fact that fumonisins can cause mycotoxicoses outbreaks in animals, are carcinogenic, and disrupt sphingolipid metabolism, have resulted in a surge in global interest in these compounds in the decade following their discovery.
This research provides a comprehensive look at the history and impact of the discovery of fumonisins, highlighting the importance of mycotoxin research in the context of public health, agriculture, and disease control.
Cite This Article
APA
Marasas WF.
(2001).
Discovery and occurrence of the fumonisins: a historical perspective.
Environ Health Perspect, 109 Suppl 2(Suppl 2), 239-243.
https://doi.org/10.1289/ehp.01109s2239 Publication
Researcher Affiliations
- Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, Tygerberg, South Africa. wally.marasas@mrc.ac.za
MeSH Terms
- Animals
- Carboxylic Acids / history
- Carboxylic Acids / isolation & purification
- Disease Outbreaks / history
- Disease Outbreaks / veterinary
- Encephalomalacia / history
- Encephalomalacia / veterinary
- Esophageal Neoplasms / chemically induced
- Esophageal Neoplasms / epidemiology
- Esophageal Neoplasms / history
- Female
- Fumonisins
- Fusarium / classification
- Fusarium / isolation & purification
- Fusarium / pathogenicity
- History, 20th Century
- Humans
- Male
- Mycoses / epidemiology
- Mycoses / history
- Mycoses / veterinary
- Mycotoxins / adverse effects
- Mycotoxins / history
- Mycotoxins / isolation & purification
- Pulmonary Edema / history
- Pulmonary Edema / veterinary
- South Africa / epidemiology
- Zea mays / microbiology
References
This article includes 45 references
- Shephard GS, van der Westhuizen L. Liquid chromatographic determination of the sphinganine/sphingosine ratio in serum.. J Chromatogr B Biomed Sci Appl 1998 Jun 12;710(1-2):219-22.
- Ross PF, Rice LG, Reagor JC, Osweiler GD, Wilson TM, Nelson HA, Owens DL, Plattner RD, Harlin KA, Richard JL. Fumonisin B1 concentrations in feeds from 45 confirmed equine leukoencephalomalacia cases.. J Vet Diagn Invest 1991 Jul;3(3):238-41.
- van der Westhuizen L, Brown NL, Marasas WF, Swanevelder S, Shephard GS. Sphinganine/sphingosine ratio in plasma and urine as a possible biomarker for fumonisin exposure in humans in rural areas of Africa.. Food Chem Toxicol 1999 Dec;37(12):1153-8.
- Marasas WF. Fumonisins: history, world-wide occurrence and impact.. Adv Exp Med Biol 1996;392:1-17.
- Jaskiewicz K, Marasas WF, Lazarus C, Beyers AD, Van Helden PD. Association of esophageal cytological abnormalities with vitamin and lipotrope deficiencies in populations at risk for esophageal cancer.. Anticancer Res 1988 Jul-Aug;8(4):711-5.
- Shephard GS, van der Westhuizen L, Thiel PG, Gelderblom WC, Marasas WF, van Schalkwyk DJ. Disruption of sphingolipid metabolism in non-human primates consuming diets of fumonisin-containing Fusarium moniliforme culture material.. Toxicon 1996 May;34(5):527-34.
- Norred WP. Fumonisins--mycotoxins produced by Fusarium moniliforme.. J Toxicol Environ Health 1993 Mar;38(3):309-28.
- Wilson TM, Ross PF, Rice LG, Osweiler GD, Nelson HA, Owens DL, Plattner RD, Reggiardo C, Noon TH, Pickrell JW. Fumonisin B1 levels associated with an epizootic of equine leukoencephalomalacia.. J Vet Diagn Invest 1990 Jul;2(3):213-6.
- Gelderblom WC, Thiel PG, Jaskiewicz K, Marasas WF. Investigations on the carcinogenicity of fusarin C--a mutagenic metabolite of Fusarium moniliforme.. Carcinogenesis 1986 Nov;7(11):1899-901.
- Rheeder JP, Marasas WF, Farina MP, Thompson GR, Nelson PE. Soil fertility factors in relation to oesophageal cancer risk areas in Transkei, southern Africa.. Eur J Cancer Prev 1994 Jan;3(1):49-56.
- Chu FS, Li GY. Simultaneous occurrence of fumonisin B1 and other mycotoxins in moldy corn collected from the People's Republic of China in regions with high incidences of esophageal cancer.. Appl Environ Microbiol 1994 Mar;60(3):847-52.
- Wang E, Norred WP, Bacon CW, Riley RT, Merrill AH Jr. Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme.. J Biol Chem 1991 Aug 5;266(22):14486-90.
- Marasas WF, Kellerman TS, Pienaar JG, Naudu00e9 TW. Leukoencephalomalacia: a mycotoxicosis of Equidae caused by Fusarium moniliforme Sheldon.. Onderstepoort J Vet Res 1976 Sep;43(3):113-22.
- Marasas WF. Fumonisins: their implications for human and animal health.. Nat Toxins 1995;3(4):193-8; discussion 221.
- Jaskiewicz K, Marasas WF, Rossouw JE, Van Niekerk FE, Heine Tech EW. Selenium and other mineral elements in populations at risk for esophageal cancer.. Cancer 1988 Dec 15;62(12):2635-9.
- Ross PF, Nelson PE, Richard JL, Osweiler GD, Rice LG, Plattner RD, Wilson TM. Production of fumonisins by Fusarium moniliforme and Fusarium proliferatum isolates associated with equine leukoencephalomalacia and a pulmonary edema syndrome in swine.. Appl Environ Microbiol 1990 Oct;56(10):3225-6.
- Ross PF, Rice LG, Plattner RD, Osweiler GD, Wilson TM, Owens DL, Nelson HA, Richard JL. Concentrations of fumonisin B1 in feeds associated with animal health problems.. Mycopathologia 1991 Jun;114(3):129-35.
- Kellerman TS, Marasas WF, Thiel PG, Gelderblom WC, Cawood M, Coetzer JA. Leukoencephalomalacia in two horses induced by oral dosing of fumonisin B1.. Onderstepoort J Vet Res 1990 Dec;57(4):269-75.
- Norred WP, Bacon CW, Porter JK, Voss KA. Inhibition of protein synthesis in rat primary hepatocytes by extracts of Fusarium moniliforme-contaminated corn.. Food Chem Toxicol 1990 Feb;28(2):89-94.
- Merrill AH Jr, Wang E, Gilchrist DG, Riley RT. Fumonisins and other inhibitors of de novo sphingolipid biosynthesis.. Adv Lipid Res 1993;26:215-34.
- Gelderblom WC, Snyman SD, Abel S, Lebepe-Mazur S, Smuts CM, Van der Westhuizen L, Marasas WF, Victor TC, Knasmu00fcller S, Huber W. Hepatotoxicity and -carcinogenicity of the fumonisins in rats. A review regarding mechanistic implications for establishing risk in humans.. Adv Exp Med Biol 1996;392:279-96.
- Gelderblom WC, Marasas WF, Jaskiewicz K, Combrinck S, van Schalkwyk DJ. Cancer promoting potential of different strains of Fusarium moniliforme in a short-term cancer initiation/promotion assay.. Carcinogenesis 1988 Aug;9(8):1405-9.
- Jaskiewicz K, van Rensburg SJ, Marasas WF, Gelderblom WC. Carcinogenicity of Fusarium moniliforme culture material in rats.. J Natl Cancer Inst 1987 Feb;78(2):321-5.
- Wilson TM, Nelson PE, Marasas WF, Thiel PG, Shephard GS, Sydenham EW, Nelson HA, Ross PF. A mycological evaluation and in vivo toxicity evaluation of feed from 41 farms with equine leukoencephalomalacia.. J Vet Diagn Invest 1990 Oct;2(4):352-4.
- Wilson TM, Nelson PE, Knepp CR. Hepatic neoplastic nodules, adenofibrosis, and cholangiocarcinomas in male Fisher 344 rats fed corn naturally contaminated with Fusarium moniliforme.. Carcinogenesis 1985 Aug;6(8):1155-60.
- Castegnaro M, Garren L, Galendo D, Gelderblom WC, Chelule P, Dutton MF, Wild CP. Analytical method for the determination of sphinganine and sphingosine in serum as a potential biomarker for fumonisin exposure.. J Chromatogr B Biomed Sci Appl 1998 Dec 11;720(1-2):15-24.
- Voss KA, Plattner RD, Bacon CW, Norred WP. Comparative studies of hepatotoxicity and fumonisin B1 and B2 content of water and chloroform/methanol extracts of Fusarium moniliforme strain MRC 826 culture material.. Mycopathologia 1990 Nov;112(2):81-92.
- Kriek NP, Marasas WF, Thiel PG. Hepato- and cardiotoxicity of Fusarium verticillioides (F. moniliforme) isolates from Southern African maize.. Food Cosmet Toxicol 1981 Aug;19(4):447-56.
- Voss KA, Norred WP, Plattner RD, Bacon CW. Hepatotoxicity and renal toxicity in rats of corn samples associated with field cases of equine leukoencephalomalacia.. Food Chem Toxicol 1989 Feb;27(2):89-96.
- Marasas WF, Kellerman TS, Gelderblom WC, Coetzer JA, Thiel PG, van der Lugt JJ. Leukoencephalomalacia in a horse induced by fumonisin B1 isolated from Fusarium moniliforme.. Onderstepoort J Vet Res 1988 Dec;55(4):197-203.
- Castegnaro M, Garren L, Gaucher I, Wild CP. Development of a new method for the analysis of sphinganine and sphingosine in urine and tissues.. Nat Toxins 1996;4(6):284-90.
- Gelderblom WC, Thiel PG, van der Merwe KJ, Marasas WF, Spies HS. A mutagen produced by Fusarium moniliforme.. Toxicon 1983;21(4):467-73.
- Jackson MA, Bennett GA. Production of fumonisin B1 by Fusarium moniliforme NRRL 13616 in submerged culture.. Appl Environ Microbiol 1990 Aug;56(8):2296-8.
- Kriek NP, Kellerman TS, Marasas WF. A comparative study of the toxicity of Fusarium verticillioides (= F. moniliforme) to horses, primates, pigs, sheep and rats.. Onderstepoort J Vet Res 1981 Jun;48(2):129-31.
- Gelderblom WC, Kriek NP, Marasas WF, Thiel PG. Toxicity and carcinogenicity of the Fusarium moniliforme metabolite, fumonisin B1, in rats.. Carcinogenesis 1991 Jul;12(7):1247-51.
- Solfrizzo M, Avantaggiato G, Visconti A. Rapid method to determine sphinganine/sphingosine in human and animal urine as a biomarker for fumonisin exposure.. J Chromatogr B Biomed Sci Appl 1997 Apr 25;692(1):87-93.
- Jaskiewicz K, Marasas WF, van der Walt FE. Oesophageal and other main cancer patterns in four districts of Transkei, 1981-1984.. S Afr Med J 1987 Jul 4;72(1):27-30.
- Marasas WF, Jaskiewicz K, Venter FS, Van Schalkwyk DJ. Fusarium moniliforme contamination of maize in oesophageal cancer areas in Transkei.. S Afr Med J 1988 Aug 6;74(3):110-4.
- Kellerman TS, Marasas WF, Pienaar JG, Naudu00e9 TW. A mycotoxicosis of equidae caused by Fusarium moniliforme sheldon. A preliminary communication.. Onderstepoort J Vet Res 1972 Dec;39(4):205-8.
- Gelderblom WC, Marasas WF, Vleggaar R, Thiel PG, Cawood ME. Fumonisins: isolation, chemical characterization and biological effects.. Mycopathologia 1992 Feb;117(1-2):11-6.
- Riley RT, Norred WP, Bacon CW. Fungal toxins in foods: recent concerns.. Annu Rev Nutr 1993;13:167-89.
- Marasas WF, Kriek NP, Fincham JE, van Rensburg SJ. Primary liver cancer and oesophageal basal cell hyperplasia in rats caused by Fusarium moniliforme.. Int J Cancer 1984 Sep 15;34(3):383-7.
- Makaula AN, Marasas WF, Venter FS, Badenhorst CJ, Bradshaw D, Swanevelder S. Oesophageal and other cancer patterns in four selected districts of the Transkei, Southern Africa:1985-1990.. Afr J Health Sci 1996 Feb;3(1):11-5.
- Gelderblom WC, Jaskiewicz K, Marasas WF, Thiel PG, Horak RM, Vleggaar R, Kriek NP. Fumonisins--novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme.. Appl Environ Microbiol 1988 Jul;54(7):1806-11.
- Harrison LR, Colvin BM, Greene JT, Newman LE, Cole JR Jr. Pulmonary edema and hydrothorax in swine produced by fumonisin B1, a toxic metabolite of Fusarium moniliforme.. J Vet Diagn Invest 1990 Jul;2(3):217-21.
Citations
This article has been cited 100 times.Secure Payments
