Deoxynivalenol and Nivalenol Toxicities in Cultured Cells: a Review of Comparative Studies.

Abstract

The in vitro studies of the toxicities of trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) including cell proliferation, cytokine secretion, and the involvement of heat shock protein 90 (Hsp90) in their toxicities were reviewed. Trichothecene mycotoxins are extremely toxic to leukocytes and leukopenia is one of the leading signs of trichothecene toxicosis, implying that trichothecenes hinder cell proliferation. Both toxins retarded proliferation of all four cell lines tested. NIV was more potent than DON in human promyelocytic leukemia cell line HL60, human lymphoblastic leukemia cell line MOLT-4, and rat aortic myoblast cell line A-10. In contrast, both toxins exhibited almost the same potencies in human hepatoblastoma cell line HepG2. While exposure to 0.3 μg/mL DON greatly induced the secretion of anti-hematopoietic cytokines CCL3 and CCL4, treatment with NIV decreased the secretion of these cytokines in HL60 cells, indicating that the toxicity mechanisms of these mycotoxins differ. Because molecular chaperone Hsp90 occupies a pivotal position in a wide range of pathological processes, the effects of an Hsp90-specific inhibitor radicicol on cytokine secretions were investigated. Radicicol counteracted the effect of DON on cytokine secretion, indicating that Hsp90 plays a crucial role in DON-induced cytokine secretion in HL60 cells. Conversely, the results of co-treatment with NIV and radicicol indicate that radicicol does not mitigate the effect of NIV. Regarding CCL3 and CCL4 secretions, DON and NIV have Hsp90-related and -unrelated mechanisms of toxicities, respectively. Taken together the results suggest that, although these toxins share similar chemical structure, there are differences in their toxic mechanisms.