Progress 10/01/00 to 09/30/05
Outputs
Fumonisin is bad for your health
Impacts
Fumonisin is bad for your health
Publications
- No publications reported this period
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Progress 10/01/03 to 09/30/04
Outputs
To date, outside of the extensive ceramide synthase studies, little is known regarding the molcular targets affected by fumonisin. We have used subtractive hybridization approaches to identify candidate genesaffected by toxin. In addition, we are using fumonisin in plant studies as an inducer of programmed cell death (pcd). Work in tomato and arabidopsis, has shown the tioxin induces hallmark features of pcd and has been used in our yest screens to identify genes that inhibit pcd and thus keep cells alive.
Impacts
The carcinogenic and toxigenic effects of the mycotoxin, fumonisin, have received increasing attention because Fusarium moniliforme (FM), the fungus which produce fumonisin, is a common inhabitant of corn. Although FM is a causative agent of stalk rot disease, the fungus and fumonisin are frequently found on healthy corn plants. Since corn and corn based food products are a common staple in the diet of livestock animals and humans, fumonisin is a serious health threat. Recent studies demonstrated fumonisin ingestion correlates with an increase of esophageal cancer in Africa and China. Fumonisin also causes equine leukoencephalomalacia, pulmonary edema in swine, and immunosuppression in cattle or poultry.
Publications
- Dickman, M.B. and Panter, S. 2004. Programmed cell death in plants during development and stress responses.pp.107-152, IN:Cell Engineering, v. 4: Apoptosis. Blackwell, UK
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Progress 10/01/02 to 09/30/03
Outputs
To date, outside of the extensive ceramide synthase studies, little is known regarding molecular targets affected by fumonisin. We now have the subtractive hybridization approach working effectively. Using this technique we have already identified (and sequenced) a number of novel targets of fumonisin and have considerably more genes to evaluate. Thus we are in an advantageous position to put the molecular pieces together of the biochemical pathways together following toxin exposure. In addition, we are using fumonisin in plant studies as an inducer odf programmed cell death. wrk in tomato and arabidopsis has shown the the toxin induces the hall,mmarks of programmed cell death and can be used to select for plant genes that interefere with this process.
Impacts
The carcinogenic and toxigenic effects of the mycotoxin, fumonisin, have received increasing attention because Fusarium moniliforme (FM), the fungus which produce fumonisin, is a common inhabitant of corn. Although FM is a causative agent of stalk rot disease, the fungus and fumonisin are frequently found on healthy corn plants. Since corn and corn based food products are a common staple in the diet of livestock animals and humans, fumonisin is a serious health threat. Recent studies demonstrated fumonisin ingestion correlates with an increase of esophageal cancer in Africa and China. Fumonisin also causes equine leukoencephalomalacia, pulmonary edema in swine, and immunosuppression in cattle or poultry.
Publications
- Panter, S. and Dickman, M.B. 2003. Programmed cell death on plants during development and stress responses. IN: Cell Engineering v. 4. Blackweel UK (In press)
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Progress 10/01/01 to 09/30/02
Outputs
In the past year, we have identified genes which are induced by fumonisin, using a PCR-based subtraction approach. Eight genes that showed high similarity (> 90%) to known mammalian genes were identified. These genes included: tumor necrosis factor type 1 receptor associated protein 2 (TRAP2), human leukemia virus receptor (GLVR1), human Scaffold attachment factor A (SAF-A) also called heterogeneous nuclear ribonucleoprotein U (hnRNP-U), human protein kinase C-binding protein (RACK7), human oligosaccharyl transferase STT3 subunit, mouse WW-domain binding protein 2 (WBP2), human fibronectin, and an unknown human clone. The ability of fumonisin to alter gene expression and signal transduction pathways may be necessary for its carcinogenic and toxic effects.
Impacts
Research on the occurrence, toxicity, and mechanism of action of fumonisin has will provide information essential to establishing the degree of exposure of humans and animals to these toxins and the extent to which they pose a threat to human and animal health
Publications
- Dickman, M.B. 2002. Comparative pathobiology/compatibility approaches in generating transgenic disease resistant crop plants. Phytoparasitia (Accepted).
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Progress 10/01/00 to 09/30/01
Outputs
In the past year, we have identified genes which are induced by fumonisin, using a PCR-based subtraction approach. Eight genes that showed high similarity (> 90%) to known mammalian genes were identified. These genes included: tumor necrosis factor type 1 receptor associated protein 2 (TRAP2), human leukemia virus receptor (GLVR1), human Scaffold attachment factor A (SAF-A) also called heterogeneous nuclear ribonucleoprotein U (hnRNP-U), human protein kinase C-binding protein (RACK7), human oligosaccharyl transferase STT3 subunit, mouse WW-domain binding protein 2 (WBP2), human fibronectin, and an unknown human clone. The ability of fumonisin to alter gene expression and signal transduction pathways may be necessary for its carcinogenic and toxic effects.
Impacts
Research on the occurrence, toxicity, and mechanism of action of fumonisin has will provide information essential to establishing the degree of exposure of humans and animals to these toxins and the extent to which they pose a threat to human and animal health
Publications
- Zhang,Y., Jones, C., and Dickman, M.B. 2001. Identification of differentially expressed genes following treatment of monkey kidney cells with the mycotoxin fumonisin B1. Food and Chemical Toxicology 39:45-53.
- Jones, C., Ciacci-Zanella, J.R., Zhang, Y, Henderson, G., and Dickman, M. 2001. Analysis of fumonisin induced apoptosis. Environmental Health Perspectives 109:1-7
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Progress 10/01/99 to 09/30/00
Outputs
We have furhtered our understanding of the mechanosm of action of fumonisin
Impacts
Fuminosin causes pulmonary edema, leukoencephalamalcia and is carcinogenic; thus is an important food safety issue
Publications
- Zhang,Y. Dickman, M.B. and Jones, C. 1999. The mycotoxin fumonisin B1 transcriptionally activates the p21 promoter through a cis acting element containing two Sp1 binding sites. Journal of Biological Chemistry 274: 12367-12371.
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Progress 10/01/97 to 09/30/98
Outputs
In our continuing studies with Fusarium moliliforme, and its mycotoxin fumonisin, we have investigated the mechanism of action of this carcinogenic, and animal disease causing toxin. In collaboration with Dr. C. Jones, our studies indicate that fumonisin B1, repressed cyclin dependent kinase 2 (CDK2) activity but induced CDK inhibitors, p21 Wafl/Cipl, p27Kipl and p57Kip2in monkey kidney cells (CV-1). In contrast, CV-1 cells transformed by simian virus 40 (SV40) are resistant to the antiproliferative or apoptotic effects of FB1. Consequently, FB1 treatment of CV-1 cells leads to cell cycle arrest and apoptosis. In this study, we demonstrate that FB1transcriptionally activates the p21 promoter. Functional analysis of the p21 promoter by reporter gene assays mapped the FB1 responsive region to -124 to -47. Dnase I footprinting analysis revealed two protected motifs which span the FB1 responsive region, -124 to -101 (footprint II) and -89 to -67 (footprint III). Further
studies demonstrated that DNA sequences from -124 to - 101 were sufficient for FB1 stimulation. DNA sequences from -124 to -101 contain two Spl binding sites, and gel shift assays provided evidence that nuclear factors specifically bind to this region. Disruption of the two Spl binding sites abrogated the binding of nuclear proteins and prevented activation by FB1. Taken together, these results suggest that Spl or Spl related proteins mediate FB1 induced activation of the p21 promoter.
Impacts
(N/A)
Publications
- No publications reported this period
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Progress 10/01/96 to 09/30/97
Outputs
In our continuing studies with Fusarium moniliforme, and its mycotoxin fumonisin, we have investigated the mechanism of action of this carcinogenic, and animal disease causing toxin. In collaboration with Dr. C. Jones, our studies indicate that fumonisin B1 affects several proteins involved in apoptosis and cell cycle progression. Fumonisin B1 induces Rb cleavage and represses protein kinase C activity in chicken cells, activates transcription of p21 (a cdk2 inhibitor) in monkey cells, and induces apoptosis through a p53 independent pathway. The p21 promoter was also mapped by deletion analysis. Effects of fumonisin are blocked by inhibitors of TNF, FAS, as well as inhibitors of ICE proteases. The widespread presence in food crops and animal feed poses a significant health risk to humans and livestock. These molecules also represent a new class of natural toxicants which should be useful as model compounds to further characterize the molecular and biochemical pathways
leading to apoptosis. It is hypothesized that the ability of fumonisin to alter signal transduction pathways is necessary for carcinogenesis.
Impacts
(N/A)
Publications
- Wang, H., Jones, C., Ciacci-Zanella, J., Holt, T., Gilchrist, D.G., Dickman, M.B. 1996. Fumonisins and AAL toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells. Proc. Natl. Acad. Sci. USA 93:3461-3465.
- Yan, K., Dickman, M.B. 1996. Isolation of a B-tubulin gene from Fusarium moniliforme that confers cold sensitive benomyl resistance. Appl. Env. Microbiol. 62:3053-3056.
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Progress 10/01/95 to 09/30/96
Outputs
In our continuing studies with Fusarium moniliforme, and its mycotoxin fumonisin, we have investigated the mechanism of action of this carcinogenic, and animal disease causing toxin. In collaboration with Dr. C. Jones, our studies indicate that fumonisin represses expression of protein kinase C(PKC) and AP-1 dependent transcription. In contrast, fumonisin stimulated a simple promoter containing a single cyclic AMP response element (CRE). In addition of fumonisin to CV-1 (monkey kidney) cells induced programmed death, characterized by the formation of DNA ladders, compaction of nuclear DNA and the subsequent appearance of apoptotic bodies. Neither toxin induced cell death, DNA ladders or apoptotic bodies in CV-1 cells expressing SV40 large antigen (COS-7) at toxin concentrations which readily killed CV-1 phase in CV-1 cells but not in COS-7 cells. Although structurally similar mycotoxins from two distinct fungal phytopathogens induce apoptosis in CV-1 cells, they may
utilize different pathways. The widespread presence of these compounds in food crops and animal feed poses a significant health risk to humans and livestock. These molecules also represent a new class of natural toxicants which should be useful as model compounds to further characterize the molecular and biochemical pathways leading to apoptosis. It is hypothesized that the ability of fumonisin to alter signal transduction pathways is necessary for carcinogenesis.
Impacts
(N/A)
Publications
- Wang, H., Jones, C., Ciacci-Zanella, J., Holt, T., Gilchrist, D.G., Dickman, M.B. 1996. Fumonisins and AAL toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells. Proc. Natl. Acad. Sci. USA 93:3461-3465.
- Yan, K., Dickman, M.B. 1996. Isolation of a B-tubulin gene from Fusarium moniliforme that confers cold sensitive benomyl resistance. Appl. Env. Microbiol. 62:3053-3056.
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Progress 01/01/95 to 12/30/95
Outputs
This project became effective Oct. 1, 1995; thus, there is no progess to report.
Impacts
(N/A)
Publications
- NO PUBLICATIONS REPORTED THIS PERIOD.
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