Principal investigator: Prof. Atte von Wright, Ph.D., Department of Biochemistry and Biotechnology, University of Kuopio, e-mail: atte.vonwright@uku.fi

Abstract Microbial aerosols in houses suffering from excessive humidity are a serious public health problem. So far the main attention has been focused to the sensitizing properties of microbes and their degradation products. However, the microbes present in problem houses (molds and actinomycetes) are known producers of bioactive secondary metabolites such as antibiotics and toxins. The role of these secondary metabolites in the sick building syndrome is still largely unknown. In a previous screen a number of fungal and actinomycete isolates from problem houses were shown to have antibiotic properties against other microbes. Some of the isolates produced unidentified compounds reacting with DNA. Because of the role of DNA-damage in tumour induction these genotoxins might present a previously unknown risk associated with indoor air. In order to evaluate this risk it is necessary to identify the compounds in question, study their genotoxic potential, their production conditions and prevalence, volatility, stability, and possible other harmful effects. The aim of the project proposed in this application is to isolate and identify some of the most potent genotoxins produced by the representative microbial isolates from problem houses. The isolation is based on the fractionation of the culture media by standard procedures (organic solvent extraction, affinity chromatography, thin layer chromatography, HPLC etc.). The activity of the fractions is monitored by their selective toxicity to a DNA-repair-deficient bacterial strain extremely sensitive to DNA-damage. A more thorough mutagenicity testing with both bacterial and mammmalian test systems is then applied to the purified fractions. Purified substances are characterized using mass spectrometry, other spectroscopic methods and NMR. When sufficient information of their chemical nature has been obtained  this can be used as a basis of their detection in actual problem houses and for a tentative risk evaluation.