A Study of Single and Combined Cytotoxic Effects of Fumonisin B1, Aflatoxin B1 and Ochratoxin a on Human Mononuclear Blood Cells using Different Cytotoxic Methods
Keywords:
cytotoxicity, synergism, additive, mononucleocytes, mycototoxins, carcinogenic, aflatoxin b1, fumonisin b1, ochratoxin a
Abstract
Several studies on cereals destined for animal or human consumption in South Africa and Africa have shown co-contaminations of mycotoxins. There is evidence to suggest that the simultaneous action of different mycotoxins at various concentrations might have synergistic, inhibitive or additive effects on human and animal cells. The aims of this study were to identify combined cytotoxic effects of three of the more commonly occurring mycotoxins (aflatoxin B1 (AFB1) fumonisin B1 (FB1) and ochratoxin A (OTA)) found in South African and other feeds using the methyl thiazoltetrazolium (MTT) cytotoxicity assay, the Comet assay and Flow Cytometry to detect apoptotic and necrotic cells after exposure to the three toxins. Human mononuclear blood cells (mononucleocytes) were exposed to the three mycotoxins both singularly and in combinations at two concentrations (5 and 40ng/ml for OTA and AFB1 and 5 and 40µg/ml for FB1) and at different exposure time of 12, 24 and 48Hours. Results obtained showed cell viability variations dependent on mycotoxin concentrations and time of exposure. In addition, synergistic effects were also observed at the higher doses of 40ng for OTA and AFB1) and 40µg/ml for FB1 of the three mycotoxins compared to combinations of lower doses. However, FB1 showed low cytotoxicity effect inducing inhibitive effect when combined with the other two mycotoxins. These results confirms the hypothesis of possibility of the three mycotoxins when combined induced with synergistic effect and imply that exposure to more than one mycotoxin might change the symptomatology and severity of effects observed during single intoxications by mycotoxins.
Downloads
- Article PDF
- TEI XML Kaleidoscope (download in zip)* (Beta by AI)
- Lens* NISO JATS XML (Beta by AI)
- HTML Kaleidoscope* (Beta by AI)
- DBK XML Kaleidoscope (download in zip)* (Beta by AI)
- LaTeX pdf Kaleidoscope* (Beta by AI)
- EPUB Kaleidoscope* (Beta by AI)
- MD Kaleidoscope* (Beta by AI)
- FO Kaleidoscope* (Beta by AI)
- BIB Kaleidoscope* (Beta by AI)
- LaTeX Kaleidoscope* (Beta by AI)
How to Cite
References
Creppy, E. Chiarappa, P.; Baudrimont, I.; Borracci, P.; Moukha, M. S.; Carratu (2004) Synergistic effects of fumonisin B1 and ochratoxin A: are in vitro cytotoxicity data predictive of in vivo acute toxicity?. 201, 15-123.
P. Njobeh, M. Dutton, A. Makun (2010) H Mycotoxins and human health: Significance, prevention and control In: Mishra AK, Tiwari A, Mishra SB and Kobayashi H (Eds), Smart Biomolecules in Medicine. 2010, 132-177.
S. Hussein, M. Brasel (2001) Toxicity, metabolism, and impact of mycotoxins on humans and animals. 167(2), 101-134. https://doi.org/10.1016/s0300-483x(01)00471-1
William, P.; Jolly, E.; Ellis, W. Gyawu, E.; Johnson, N. Robinson, T. AG.; Phillips (2010) HIV and hepatocellular and esophageal carcinomas related to consumption of mycotoxin-prone foods in sub-Saharan Africa. 92, 154-160.
Paul Turner, Sophie Moore, Andrew Hall, Andrew Prentice, Christopher Wild (2003) Modification of immune function through exposure to dietary aflatoxin in Gambian children Environ. 111(2), 217-220. https://doi.org/10.1289/ehp.5753
Gong, Y. Hounsa, A.; Egal, S.; Turner, P. Sutcliffe, A. Cardwell, C. K.; Wild (2004) Post-weaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa Environ. 112, 1334-1338.
Williams Phillips, T. Jolly, P. Stiles, J. Jolly, D. C.M.; Aggarwal (2004) Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences and interventions Am J Clin. 80, 1106-1122.
J. Wagacha, J. Muthomi (2008) Mycotoxin problem in Africa current status implications to food safety and health and possible management strategies Inter J. 124(1), 1-12. https://doi.org/10.1016/j.ijfoodmicro.2008.01.008
R. Riley (1998) Mechanistic interactions of mycotoxins: theoretical consideration In: Sinha, K.K., Bhatnagar, D (Eds.), Mycotoxins in Agriculture and Food Safety. 1998, 227-254.
Yoo, H. Norred, Riley W.P.; Showker (1996) R.T.Elevated sphingoid bases and complex sphingolipid depletion as contributing factors in fumonisin-induced cytotoxicity.Toxicol& Appl. 138, 211-218.
A. Merrill (1997) Jr.; Schmelz, E.M.; Dillehay, D.L.; Spiegel, S.; Shayman, J.A.; Schroeder, J.J.; Riley, R.T.; Voss, K.A.; Wang, E Sphingolipids: The enigmatic lipid class: Biochemistry, Physiology and Pathophysiology Toxicol Appl. 142, 208-225.
G. Shephard, L. Van der Westhuizen (1998) Liquid chromatographic determination of the sphinganine/sphingosine ratio in serum. 710, 219-222.
W. Marasas, K. Jaskiewics, F. Venter, D. VanSchalkwyk (1988) Fusarium moniliforme contamination of maize in oesophageal cancer areas in Transkei S A Med J. 74, 110-114.
G. Diaz, H. Boermans (1994) Boermans, H.J., Fumonisin toxicosis in domestic animals: a review Vet. 36, 548-555.
Ueno, Y.; Lijima, K.; D-Wang, S. Sugiura, Y.; Sekijima, T.; Tanaka, T.; Chen, S. C.; Yu (1997) Fumonisins as a possible contributory risk factor for primary liver cancer: A 3-year study of corn harvested in Haimen, China, by HPLC and ELISA Food Chem. 35, 1143-1150.
J. Fincham, W. Marasas, J. Taljaard, N. Kriek, C. Badenhorst, W. Gelderblom, J. Seier, C. Smuts, M. Faber, M. Weight (1992) Atherogenic effects in a non-human primate of cultures added to a carbohydrate diet. 94(1), 13-25. https://doi.org/10.1016/0021-9150(92)90183-h
Michael Dutton (2009) The African Fusarium/maize disease.Mycotox Res. 25(1), 29-39. https://doi.org/10.1007/s12550-008-0005-8
Janee Gelineau‐van Waes, Lois Starr, Joyce Maddox, Francisco Aleman, Kenneth Voss, Justin Wilberding, Ronald Riley (2005) Maternal fumonisin exposure and risk for neural tube defects: Mechanisms in an in vivo mouse model Birth Defects Research A: Clin Mol. 73(7), 487-497. https://doi.org/10.1002/bdra.20148
Stacey Missmer, Lucina Suarez, Marilyn Felkner, Elaine Wang, Alfred Merrill, Kenneth Rothman, Katherine Hendricks (2006) Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border Environ. 114(2), 237-241. https://doi.org/10.1289/ehp.8221
G. Devegowda, M. Radu, A. Nazar, H. Swamy (2000) Mycotoxin picture worldwide: Novel solutions for their counteraction.
Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. 82.
Lillerberg, S. Cabonce, M. Raju, N. Wagner, L. L.M.; Kier (1992) Alterations in the p53 tumour suppressor gene in rat liver tumours induced by aflatoxin B1 Program.Clin Biol. 376, 203-222.
Aguilar, F.; Hussdain, P. S.P.; Cerutti (1993) Aflatoxin B1 induces the transversion of G-->T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. 1993, 8586-8590.
Y. Gong, S. Egal, A. Hounsa, P. Turner, A. Hall, K. Cardwell, C. Wild (2003) Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning Food Res. 37, 985-1000.
(1993) Monographs on the evaluation of the carcinogenic risk of chemicals to human: Some naturally occurring substances. Food items and constituents, heterocyclic aromatic amines and mycotoxins. 1993, 397-444.
E. Creppy (1983) Comparative study of the effect of ochratoxin A analogues on yeast aminoacyltRNAsynthetases and on the growth and protein synthesis of hepatoma cells Toxicol. 19(3), 217-224. https://doi.org/10.1016/0378-4274(83)90122-4
R. Manderville (2007) Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans. 51, 61-99.
Evaluation of Certain Mycotoxins in Food.
P. Mantle, V. Faucer-Marquis, R. Manderville, B. Squillaci (2010) Pfohl-Leszkowicz, A., Structures of covalent adducts between DNA and ochratoxin A: a new factor in debate about genotoxicity and human risk assessment Chem Res.Toxicol. 23(1), 89-98. https://doi.org/10.1021/tx900295a
Stoev, S. etiology, prophylaxis, humans (2008) Complex Etiology, Prophylaxis and Hygiene Control in Mycotoxic Nephropathies in Farm Animals and Humans. 9, 578-605.
Stoev, S. Denev, S.; Njobeh, P. Mosonik, J. Steenkamp, P. Petkov (2010) Complex etiology and pathology of mycotoxic nephropathy in South African pigs. 10, 31-46.
S. Stoev (2008) Mycotoxic nephropathies in farm animals' diagnostics, risk assessment and preventive measures. 155-195.
J. Fink‐gremmels, L. Leistner (1990) Toxicological evaluation of moulds. 4(1), 579-584. https://doi.org/10.1080/08905439009549772
S. Stoev, S. Denev, M. Dutton, B. Nkosi (2009) Cytotoxic Effect of Some Mycotoxins and their Combinations on Human Peripheral Blood Mononuclear Cells as Measured by the MTT Assay Toxinol J. 2(1), 1-8. https://doi.org/10.2174/1875414700902010001
Mwanza, M.; Kametler, L.; Bonais, A.; Rajli, M. V.; Kovacs, M. Dutton (2009) The cytotoxic effect of fumonisin B1 and ochratoxin A on human and pig lymphocytes using the Methyl Thiazol Tetrazolium (MTT) assay. 25, 233-238.
F. Meky, L. Hardie, S. Evans, C. Wild (2001) Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production Food Chem Toxicol. 39(8), 827-836. https://doi.org/10.1016/s0278-6915(01)00029-1
Narendra Singh, Michael McCoy, Raymond Tice, Edward Schneider (1988) A simple technique for quantitation of low levels of DNA damage in individual cells.Experiment Cell Res. 175(1), 184-191. https://doi.org/10.1016/0014-4827(88)90265-0
Collins, A. Oscoz, A. Brunborg, G.; Gaivao, I.; Giovannelli, L.; K (1997) The comet assay: topical issues. 23(3), 143-151. https://doi.org/10.1093/mutage/gem051
A. Hartmann, E. Agurell, C. Beevers, S. Brendler- Schwaab, B. Burlinson, P. Clay (2003) Clay, P., 2003: Recommendations for conducting the in vivo alkaline Comet assay. 18(1), 45-51. https://doi.org/10.1093/mutage/18.1.45
P. Delves, Seamus M., D. Burton, Y. Roitt (2006) Roitt's essential immunology. 2006, 496.
K. Charoenpornsook, J. Fitzpatrick, J. Smith (1998) The effects of four mycotoxins on the mitogen stimulated proliferation of bovine peripheral blood mononuclear cells in vitro. 143(2), 105-111. https://doi.org/10.1023/a:1006971724678
Mary Dombrink-Kurtzman, Tariq Javed, Glenn Bennett, John Richard, L. Cote, William Buck (1993) Lymphocyte cytotoxicity and erythrocytic abnormalities induced in broiler chicks by fumonisins B1 and B2 and moniliformin from Fusarium proliferatum. 124(1), 47-54. https://doi.org/10.1007/bf01103056
Grabsch, G.; Wichmann, G.; Loffhagen, H.; Herbarth, A. O.; Muller (2006) Cytotoxicity assessment of gliotoxin and penicillic acid in Tetrahymenapyriformis, Environ. 2, 111-117.
C. Lewis, J. Smith, J. Anderson, R. Freshney (1999) Increased cytotoxicity of food-borne mycotoxins toward human cell lines in vitro via enhanced cytochrome p450 expression using the MTT bioassay. 148, 97-102.
J. Timbrell (2001) Toxic responses to foreign compounds In Principles of Biochemical Toxicology, 3rd ed. 2001, 240-247.
F. Kiechle (2004) The omics era and its impact. 128, 1337-1345.
D. Vinatier, P. Dufour, D. Subtil (1996) Apoptosis: a programmed cell death involved in ovarian and uterine physiology European J Obstetric Gynaecol Repro Biol. 67(2), 85-102. https://doi.org/10.1016/0301-2115(96)02467-0
Domijan, A.; Zeljezic, D.; Kopjar, M. N.; Peraica (2006) Standard and Fpg-modified comet assay in kidney cells of ochratoxin Aand fumonisin B1-treated rats. 222(1-2), 53-59. https://doi.org/10.1016/j.tox.2006.01.024
Peter Lutz, Liscia Manuel (1999) Maintenance of adenosine A1receptor function during long-term anoxia in the turtle brain. 276(3), R633-R636. https://doi.org/10.1152/ajpregu.1999.276.3.r633
Mário Mantovani, Marilanda Bellini, José Angeli, Rodrigo Oliveira, Ariane Silva, Lúcia Ribeiro (2008) β-Glucans in promoting health: Prevention against mutation and cancer Mutation Res. 658(3), 154-161. https://doi.org/10.1016/j.mrrev.2007.07.002
F. Minervini, F. Fornelli, K. Flynn (2004) Toxicity and apoptosis induced by the mycotoxins nivalenol, deoxynivalenol and fumonisin B1 in a human erythroleukemia cell line. 18(1), 21-28. https://doi.org/10.1016/s0887-2333(03)00130-9
M. Theumer (2003) Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats. 186(1-2), 159-170. https://doi.org/10.1016/s0300-483x(02)00603-0
W. Butler, G. Neal (1977) Mode of action and human health aspects of aflatoxin carcinogenesis.
E. Lillehoj (1991) Aflatoxin: an ecologically elicited activation signal. 1991, 119-139.
L. Foster, K. Kozack, M. Loftus (1993) Steven, J., The polymerase chain reaction and its application to filamentous fungi. 97(7), 769-781. https://doi.org/10.1016/s0953-7562(09)81148-9
Raney, K. Meyer, D. Ketterer, B.; Harris, F. T.M.; Guengerish (1992) Glutathione conjugation of aflatoxin B1 exo- and endo-epoxides by rat and human glutathione S-transferases. 5, 470-478.
Yau-Huei Wei, Ching-Yow Lu, Teng-Nan Lin, Ru-Dong Wei (1985) Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation. 36(2-3), 119-130. https://doi.org/10.1016/0300-483x(85)90046-0
C. Wild, P. Turner The toxicology of aflatoxins as a basis for public health decisions.
Voss, K. Howard, P. Riley, R. Bucci, T. Lorentzen (2002) R.J Carcinogenicity and mechanism of action of fumonisin B1: a mycotoxin produced by Fusarium moniliforme (=F verticillioides) Cancer Detection Prev. 26(1), 1-9. https://doi.org/10.1016/s0361-090x(02)00011-9
W. Seefelder (2003) Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites Toxicol Appl. 192, 146-153.
CAST (2003) Mycotoxins: Risks in Plant, Animal, and Human Systems. 199. https://doi.org/10.62300/n5iy3v52
E. Wang, W. Norred, C. Bacon, R. Riley, A. Merrill (1998) Merrill, A.H Jr Inhibition of sphingolipids biosynthesis by fumonisin J Biol. 273, 1025-1103.
G. Bondy, J. Pestka (2000) Immunomodulation by fungal toxins Environ. 2000, 109-143.
Martynova (2005) Fumonisin B1 modulates sphingomyelin cycle product levels and the expression of CD3 receptors in immunocompetent organs. 2005, 93-137.
Published
2014-03-13
Issue
Section
License
Copyright (c) 2014 Authors and Global Journals Private Limited

This work is licensed under a Creative Commons Attribution 4.0 International License.