Submitted to: Toxicological Sciences
Publication Type: Review Article
Publication Acceptance Date: 11/7/2009
Publication Date: 2/1/2010
Citation: Voss, K.A. 2010. A new perspective on deoxynivalenol and growth suppression. Toxicological Sciences 113(2):281-283. Interpretive Summary: Deoxynivalenol (DON) is a mycotoxin produced by Fusarium molds that gtow on crops. It is found in cereal grains, feeds and foods and causes various toxic effects in farm and laboratory animals including vomiting, loss of appetite, and reduced growth rates. The risk of DON to humans is poorly understood however surveys have shown that DON exposure sometimes exceeds the recommended daily amounts considered to be safe (PMTDI = provisional maximum tolerated daily intake), Reduced growth in mice fed DON over a two year period was the critical finding for determining the PMTDI, however, it is not known how DON impairs weight gain. New findings by Amouzie et al. suggest that DON reduces growth in mice by disrupting specific molecular signaling pathways. These pathways, which lead to reduced growth hormone signaling to the tissues, and the specific steps in these pathways affected by DON, are reviewed. Their results emphasize the role of a key molecule found in serum known as the insulin-like growth factor acid labile subunit or IGFALS. The findings also suggest that monitoring IGFALS in serum might serve as a useful biomarker of DON for epidemiological and further laboratory studies designed to better understand the potential risks of DON to consumers.
Technical Abstract: Deoxynivalenol (DON) is a trichothecene produced by Fusarium species. It is found in cereal grains, feeds and foods and exerts various toxic effects in farm and laboratory animals. These include vomiting, loss of appetite, and growth suppression. Surveys have shown that DON intake by consumers, including infants, of cereal products sometimes exceeds the provisional maximum tolerated daily intake (PMTDI) of 1 µg DON/kg body weight. Growth suppression in mice fed diets containing > 5 ppm DON for 2 years was a critical finding for determining the PMTDI, however, the mechanisms underlying this effect are poorly understood. Novel findings by Amouzie et al. suggesting that DON suppresses growth in mice by interfering with growth hormone-dependent signaling are reviewed. Their findings suggest DON suppresses growth through a mechanism involving negative regulation of the growth hormone receptor complex by suppressors of cytokine signaling (SOCS) leading to decreased levels of circulating insulin-like growth factor acid labile subunit or IGFALS. The latter is a key protein that acts to stabilize a critical pro-growth signaling protein complex in serum . The proposed mechanism is consistent with and connects both the known effects of DON on cytokine-mediated signaling and the regulation of growth hormone-dependent signaling pathways by SOCS and IGFALS. Their results further suggest that serum concentrations of IGFALS might also serve as a mechanism-based biomarker of DON exposure for epidemiological and laboratory studies to better understand the potential risks of DON to consumers.