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Published on: August 25, 2013
Tissue sphinganine as a biomarker of fumonisin-induced apoptosis
1National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA. rdelongchamp@nctr.fda.gov
Abstract:
NCTR measured sphinganine concentrations in the livers of mice and in the livers and kidneys of rats in conjunction with a tumour bioassay. In our model of the tumour incidence, target-tissue levels of sphinganine serve as a biomarker for a dose response of fumonisin B1 on cell death. Initially we questioned the utility of sphinganine levels in this role because they were highly variable when compared across time points. In spite of this concern, a conceptual framework and data are presented that support the use of sphinganine as a biomarker for a dose response of fumonisin B1 on cell death. This framework is reasonably consistent with observed sphinganine concentrations in the examined tissues, the literature on fumonisin's effects on sphingolipid synthesis, and our hypothesized mechanism through which fumonisin B1 increases age-specific tumour incidence.
Insights
Sphinganine levels in animal tissues can serve as a biomarker for fumonisin B1 exposure, indicating a dose-response relationship with cell death and tumor incidence. This research supports sphinganine
Area of Science:
- Toxicology
- Biochemistry
- Cancer Research
Background:
- Fumonisin B1 (FB1) is a mycotoxin linked to increased tumor incidence.
- Sphingolipid metabolism is a known target of FB1.
- Sphinganine is a key intermediate in sphingolipid synthesis.
Purpose of the Study:
- To evaluate sphinganine as a biomarker for FB1-induced cell death.
- To establish a dose-response relationship between FB1 and sphinganine levels.
- To investigate the role of sphinganine in FB1-mediated tumor formation.
Main Methods:
- Measurement of sphinganine concentrations in mouse and rat tissues (liver, kidney).
- Tumor bioassay in conjunction with sphinganine level analysis.
- Development of a conceptual framework linking sphinganine levels to FB1 dose-response.
Main Results:
- Sphinganine concentrations were measured in target tissues.
- Despite initial variability, a conceptual framework supports sphinganine's utility as a biomarker.
- Observed sphinganine levels align with known FB1 effects on sphingolipid synthesis.
Conclusions:
- Sphinganine is a viable biomarker for FB1-induced cell death.
- The study provides a framework consistent with FB1's mechanism of increasing tumor incidence.
- Further research can utilize sphinganine to understand FB1 toxicology.
