The induction and persistence of altered sphingolipid biosynthesis in rats treated with fumonisin B1.
The fumonisins produced by Fusarium spp. are carcinogenic in rodents and possibly carcinogenic to humans. One action of fumonisins is to inhibit the enzyme ceramide synthase and as a consequence disrupt de novo sphingolipid biosynthesis. Measurement of the ratio of sphinganine (Sa) to sphingosine (So) in urine, serum and tissues has thus been made in various animal species as a marker of exposure to this mycotoxin. In this study in male BDIV rats, the effect of increasing daily gavage doses (0.01-5 mg/kg b.w.) of fumonisin B1 (FB1) on the Sa/So ratio in various tissues and urine was examined as was the persistence of the effects after cessation of treatment. The lowest dose of FB1 which induced an alteration of Sa/So in any tissue was 1 mg/kg b.w. The tissue most affected was the kidney, with the liver affected to a much lesser extent and the lung and oesophagus not at all. Only a modest indication of an alteration in Sa/So ratio was obtained in the urine. The large interindividual variations in urinary Sa and So in this strain of rat, even in the absence of FB1 treatment, made interpretation of these data difficult. After cessation of treatment, the Sa/So ratio returned to normal in kidney after a period of 1-3 weeks. These data suggest that altered Sa/So ratios reflect recent exposure to FB1 in the rat.
Garren
L
L
Unit of Gene-Environment Interactions, International Agency for Research on Cancer, Lyon, France.
Galendo
D
D
Wild
C P
CP
Castegnaro
M
M
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002264:Carboxylic Acids / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism; D037341:Fumonisins; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009183:Mycotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000096:biosynthesis*
D015415:Biomarkers; D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D004791:Enzyme Inhibitors; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol