Tissue sphinganine as a biomarker of fumonisin-induced apoptosis.
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.
Delongchamp
R R
RR
National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA. rdelongchamp@nctr.fda.gov
Young
J F
JF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D002264:Carboxylic Acids / Q000097:blood / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D005506:Food Contamination; D037341:Fumonisins; D006207:Half-Life; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009183:Mycotoxins / Q000097:blood / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D015415:Biomarkers; D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D004791:Enzyme Inhibitors; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D011493:Protein Kinase C; D013110:Sphingosine; C005682:safingol