ToxSci Advance Access published online on November 15, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm284
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Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building-Related Illness: New Insights into a Public Health Enigma
1 Center for Integrative Toxicology 2 Department of Microbiology and Molecular Genetics 3 Department of Food Science and Human Nutrition,Michigan State University, East Lansing, MI 48824 4 Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, OH 44106 5 U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 6 Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824
* To whom all correspondence should be addressed: J.J. Pestka, 234 G.M. Trout Building, Michigan State University, East Lansing, MI 48824-1224, USA. Telephone: (517) 353-1709. Fax: (517) 353-8963, Email: Pestka{at}msu.edu.
Received September 26, 2007; revision received November 9, 2007; accepted November 9, 2007
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Abstract |
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Damp building-related illnesses (DRBI) include a myriad of respiratory, immunologic and neurologic symptoms that are sometimes etiologically linked to aberrant indoor growth of the toxic black mold, Stachybotrys chartarum. Although supportive evidence for such linkages are limited, there are exciting new findings about this enigmatic organism relative to its environmental dissemination, novel bioactive components, unique cellular targets and molecular mechanisms of action which provide insight into the S. chartarum's potential to evoke allergic sensitization, inflammation and cytotoxicity in the upper and lower respiratory tracts. Macrocyclic trichothecene mycotoxins, produced by one chemotype of this fungus, are potent translational inhibitors and stress kinase activators that appear to be a critical underlying cause for a number of adverse effects. Notably, these toxins form covalent protein adducts in vitro and in vivo and, furthermore, cause neurotoxicity and inflammation in the nose and brain of the mouse. A second S.chartarum chemotype has recently been shown to produce atranones - mycotoxins that can induce pulmonary inflammation. Other biologically active products of this fungus that might contribute to pathophysiologic effects include proteinases, hemolysins, ß-glucan and spirocyclic drimanes. Solving the enigma of whether Stachybotrys inhalation indeed contributes to DRBI will require studies of the pathophysiologic effects of low dose chronic exposure to well-characterized, standardized preparations of S. chartarum spores and mycelial fragments, and, co-exposures with other environmental cofactors. Such studies must be linked to improved assessments of human exposure to this fungus and its bioactive constituents in indoor air using both state-of-the-art sampling/analytical methods and relevant biomarkers.
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