Date of Award
Doctor of Philosophy
Gary D. Osweiler
Tetrazolium salt cleavage test (MTT), a rapid colorimetric assay, was used to study the mechanisms involved in the cytotoxicity of Fumonisins (FB) in cell culture. Cell lines used were derived from reported organs susceptible to FB toxicity. The cell lines were: BNL-CL2, CL9, LLC-PK[subscript]1, and L2 derived from mouse liver, rat liver, pig kidney, and rat lung respectively. Cells grown in medium containing 0.1% Sodium Phenobarbital or using an S9-mix, a source of microsomal mixed function oxidase enzymes, did not significantly (P > 0.05) increase the cytotoxicity of fumonisin B[subscript]1 (FB[subscript]1) or a crude extract (C[subscript]8) of FB (B[subscript]1, B[subscript]2, and B[subscript]3) in BNL-CL2 cells. Glutathione (GSH) depletion by 0.5mM diethyl maleate significantly (P < 0.0001) increased the cytotoxicity of FB in all cell lines. The increase ranged from 3.3 to greater than 20-fold in L2 and BNL-CL2 respectively;Comparison of 3 levels of both natural antioxidant vitamin E and phenolic antioxidant (3-tert-butyl-4-) hydroxyanisole (BHA), significantly (P < 0.0001) reduced the cytotoxicity of FB in BNL-CL2 and L2 cell lines. The protective effect was significantly higher (P < 0.001) in GSH depleted cells. These findings suggest that the mechanism of FB toxicity may be caused by the parent compound and FB cytotoxicity is related to the GSH content of cells. Also, FB cytotoxicity may involve the generation of reactive intermediates, leading possibly to lipid peroxidation. GSH and antioxidants are known to protect cells from such damages. Thus, the use of antioxidants in FB contaminated feeds should reduce the toxicity of FB in animals.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Charles E. Azuka
Azuka, Charles E., "Cellular toxicity of Fumonisins " (1992). Retrospective Theses and Dissertations. 9972.