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ToxSci Advance Access originally published online on November 15, 2007
Toxicological Sciences 2008 104(1):4-26; doi:10.1093/toxsci/kfm284
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building–Related Illness: New Insights into a Public Health Enigma

James J. Pestka*,{dagger},{ddagger},1, Iwona Yike§, Dorr G. Dearborn§, Marsha D. W. Ward and Jack R. Harkema*,||

* Center for Integrative Toxicology {dagger} Department of Microbiology and Molecular Genetics {ddagger} Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824 § Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, Ohio 44106 U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 || Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824

1 To whom all correspondence should be addressed at 234 G.M. Trout Building, Michigan State University, East Lansing, MI 48824-1224. Fax: (517) 353-8963. E-mail: Pestka{at}msu.edu.

Received September 26, 2007; accepted November 9, 2007


   Abstract

Damp building–related illnesses (DBRI) 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 is 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, β-glucan, and spirocyclic drimanes. Solving the enigma of whether Stachybotrys inhalation indeed contributes to DBRI 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, coexposures 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.

Key Words: lung; respiratory system; nervous system; neurotoxicology; nose; respiratory toxicology; natural products; agents; inflammation; immunotoxicology.


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