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ToxSci Advance Access published online on December 1, 2004

Toxicological Sciences, doi:10.1093/toxsci/kfi045
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received August 17, 2004
Accepted November 15, 2004

Environmental Toxicology

Stachybotrys Chartarum Alters Surfactant-Related Phospholipid Synthesis and CTP:Cholinephosphate Cytidylyltransferase Activity in Isolated Fetal Rat Type II Cells

C. Hastings 1, T. Rand 2, H. T. Bergen 3, J. A. Thliveris 3, A. Shaw 4, G. A. Lombaert 5, H. H. Mantsch 4, B. L. Giles 6, S. Dakshinamurti 7, and J. E. Scott 8*

1 Department of Oral Biology, Faculty of Dentistry & Medicine, University of Manitoba, Winnipeg, Manitoba
2 Department of Biology, St. Mary's University, Halifax, Nova Scotia
3 Department of Human Anatomy and Cell Science, Faculty of Dentistry & Medicine, University of Manitoba, Winnipeg, Manitoba
4 The National Research Council, Institute for Biodiagnostics, Winnipeg, Manitoba
5 Health Canada, Health Products and Food Branch, Winnipeg, Manitoba
6 The Manitoba Institute of Child Health, Biology of Breathing Group, Children's Hospital Foundation, Winnipeg, Manitoba, Manitoba
7 The Manitoba Institute of Child Health, Biology of Breathing Group, Children's Hospital Foundation, Winnipeg, Manitoba
8 Department of Oral Biology, Faculty of Dentistry & Medicine, University of Manitoba, Winnipeg, Manitoba; Department of Human Anatomy and Cell Science, Faculty of Dentistry & Medicine, University of Manitoba, Winnipeg, Manitoba; The Manitoba Institute of Child Health, Biology of Breathing Group, Children's Hospital Foundation, Winnipeg, Manitoba

* To whom correspondence should be addressed.
J. E. Scott, E-mail: jscott{at}ms.umanitoba.ca


   Abstract

S. chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabelled with [3H]choline and incubated with spore extract showed decreased incorporation of [3H]choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.

Keywords: lung; mold spores; cytidylyltransferase; surfactant.
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