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DNA-damage and cytogenetic effets of ochratoxin A in different cultured cells in the presence and absence of metabolic activation and in rats treated with ochratoxin A in vivo

Exposure of rats to OTA by feed for a period of time 6 months (mean serum OTA 7 mg/ml) resulted in slight genetic damage in some tissues and organs. Increases in the “tail moment values” of “comets” observed in the liver and bone marrow reflect the induction of primary DNA lesions.

Bone marrow, spleen, liver, kidney and whole blood of rats treated for 15 month with OTA in food only showed marked increases in DNA breakage in kidney. The effect was amplified by Fpg indicating unprepared oxidative damage which is not converted into permanent cytogenetic damage as evinced by the absence of clastogenicity in G0 resting splenocytes from spleen of treated rats and stimulated with concanavalin-A (Con-A) to grow in vitro.

Negative results in terms of clastogenicity were also obtained in animals treated by oral gavage at 250, 500, 1000 and 2000ug/kg for 5 days per week for 2 weeks consecutively, though the spectra of induced primary DNA lesions was differ in the different organ/tissues analysed.

In vitro studies show that OTA does not induce chromosomal aberrations and SCE's, but an increase in the frequencies of both endoreduplicated and polyploid cells. Since OTA in vitro does not show cytogenetic activity we evaluated the possibility whether the induction of endoreduplication was caused by a possible activity of OTA on the cell cycle. Endoreduplication is not induced via inhibition of mictrotubuli and can be caused by interference of OTA with cell cycle progression. Metabolically competent cell lines treated with OTA did not show increased frequencies of micronuclei indicating no role of bioactivation.

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Università degli Studi della Tuscia, Viterbo
Via San Camillo de Lellis s.n.c.
01100 Viterbo
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