Fumonisin B(1): oxidative status and DNA damage in rats.
Fumonisin B(1) (FB(1)) is a carcinogenic mycotoxin involved in several animal diseases and assumed to be involved in the etiology of some human tumors. FB(1) disturbs the metabolism of sphinganine (Sa) and sphingosine (So), increasing the ratio of their concentrations (Sa/So). FB(1) is mutagenic in cell cultures, but the mechanism of its genotoxicity is not understood. The aim of this study was to see whether DNA lesions in kidney and liver cells of rats treated with FB(1) were related to the changes in the oxidative status or to the disturbance of the sphingolipid metabolism. Male Wistar rats were receiving either FB(1) (0.5 mg/kg b.w./day, i.p. for 2 or 7 days) or solvent only and were sacrificed 24 h after the last treatment. The ratio of Sa and So concentrations and parameters of oxidative status (catalytic activity of catalase and the concentrations of protein carbonyls and malondialdehyde, MDA) were measured in plasma and liver and kidney homogenates, while DNA damage was measured in liver and kidney using the comet assay. In plasma and liver and kidney homogenates catalase activity and the concentrations of protein carbonyls and MDA were not affected by the 2-day treatment with FB(1), but the ratio of Sa and So in plasma and liver and kidney homogenates was significantly higher than in controls (0.99+/-0.27 versus 0.38+/-0.08, 1.05+/-0.12 versus 0.59+/-0.09 and 4.51+/-0.51 versus 0.54+/-0.17, respectively) (p<0.05). After the 2-day treatment, the tail length and tail intensity measured with the comet assay in the liver homogenate did not change, while in the kidney homogenate, the difference between the treated and control animals was significant in both the tail length (26.4+/-0.7 microm versus 14.6+/-0.1 microm) and tail intensity (8.0+/-0.4% versus 1.7+/-0.02% DNA) (p<0.05). After the 7-day treatment all measured parameters significantly differed from controls (p<0.05). This study showed that FB(1) causes DNA lesions in the kidney of experimental animals before affecting the catalytic activity of catalase and the concentration of protein carbonyls and MDA. The ratio of Sa and So significantly increases in all tissues already after 2-day treatment thus indicating that the metabolism of sphingolipids may have an important role in the DNA damage caused by FB(1).
Domijan
Ana-Marija
AM
Unit of Toxicology, Institute for Medical Research and Occupational Health, Ksaverska c. 2, 10000 Zagreb, Croatia. adomijan@imi.hr
Zeljezić
Davor
D
Milić
Mirta
M
Peraica
Maja
M
D000818:Animals; D002374:Catalase / Q000097:blood; D020552:Comet Assay; D004249:DNA Damage / Q000502:physiology*; D037341:Fumonisins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D015162:Micronucleus Tests; D009183:Mycotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives / Q000097:blood
D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D008315:Malondialdehyde; D002374:Catalase; D013110:Sphingosine; C005682:safingol