Health Effects of Stachybotrys – Toxic Interactions

 

 

This page lists medical journal articles discussing toxic interactions associated with Stachybotrys exposures.

The Health Effects of Stachybotrys Chartarum page of the Paradigm Change site provides further information on the effects of this toxic mold.

 

Markkanen PP, Pelkonen J, Tapanainen M, Mäki-Paakkanen J, Jalava PI, Hirvonen MR. Co-cultivated damp building related microbes Streptomyces californicus and Stachybotrys chartarum induce immunotoxic and genotoxic responses via oxidative stress. Inhalation toxicology. 2009;21:857–867. PMID: 19459771

The capability of Streptomyces californicus and Stachybotrys chartarum to induce oxidative stress was evaluated in vitro. All the studied microbial exposures triggered oxidative stress and subsequent cellular damage in RAW264.7 macrophages. The ROS scavenger, NAC, prevented growth arrest, apoptosis, DNA damage, and cytokine production induced by the co-culture since it reduced the intracellular level of ROS within macrophages. In contrast, the DNA damage and cell cycle arrest induced by the spores of S. californicus alone could not be prevented by NAC. The researchers conclude that microbial interactions during co-cultivation stimulate the production of highly toxic compound(s) which may significantly increase oxidative damage.

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Penttinen Piia, Tampio Marjo, Mäki-Paakkanen Jorma, Vähäkangas Kirsi, Pelkonen Jukka, Hirvonen Maija-Riitta R.. DNA damage and p53 in RAW264.7 cells induced by the spores of co-cultivated Streptomyces californicus and Stachybotrys chartarum. Toxicology. 2007;235:92–102. PMID: 17420079

Our recent studies have revealed that the co-cultivation of environmental microbes, Streptomyces californicus and Stachybotrys chartarum, potentiates the immunotoxic properties of the spores. In the present study, the spore-induced genotoxic potential of these microbes was investigated. The results revealed that the spores of co-cultivated microbes evoked DNA damage, p53 accumulation and cytotoxicity at a lower dose than the other exposures, and at the highest dose there was a 2.5-fold increase in DNA damage compared to control. In addition, the spores of Streptomyces californicus alone induced a 1.5-fold increase in DNA damage compared to control, dose dependent p53 accumulation and also extensive cytotoxicity. In contrast, the mixture of separately cultivated spores or the spores of Stachybotrys chartarum alone did not induce DNA damage with any tested dose although they triggered significant cytotoxicity and a slightly increased p53 level.

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Penttinen P, Pelkonen J, Huttunen K, Hirvonen MR. Co-cultivation of Streptomyces californicus and Stachybotrys chartarum stimulates the production of cytostatic compound(s) with immunotoxic properties. Toxicology and applied pharmacology. 2006;217:342–351. PMID: 17095029

The present data indicate that interactions during co-cultivation of S. californicus and S. chartarum stimulate the production of an unidentified cytostatic compound(s) capable of inducing mitochondria mediated apoptosis and cell cycle arrest at S-G(2)/M. The spores of co-cultivated microbes caused a 4-fold collapse of mitochondrial membrane potential and an almost 6-fold caspase-3 activation and DNA fragmentation when compared to control. These data suggest that when growing in the same habitat, interactions between S. californicus and S. chartarum stimulates the production of an unknown cytostatic compound(s) which evoke immunotoxic effects similar to those by chemotherapeutic drugs.

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Penttinen P, Pelkonen J, Huttunen K, Toivola M, Hirvonen MR. Interactions between Streptomyces californicus and Stachybotrys chartarum can induce apoptosis and cell cycle arrest in mouse RAW264.7 macrophages. Toxicology and applied pharmacology. 2005;202:278–288. PMID: 15667833

Co-culture of S. californicus and S. chartarumcan result in microbial interactions that significantly potentiate the ability of the spores to cause apoptosis and cell cycle arrest in mammalian cells.

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Penttinen P, Huttunen K, Pelkonen J, Hirvonen MR. The proportions of Streptomyces californicus and Stachybotrys chartarum in simultaneous exposure affect inflammatory responses in mouse RAW264.7 macrophages. Inhalation toxicology. 2005;17:79–85. PMID: 15764485

In this study, we aimed to evaluate the effects of simultaneous exposure with modified proportions of actinobacteria Streptomyces californicus and fungi Stachybotrys chartarum on inflammatory responses (cytokines macrophage inflammatory protein 2 [MIP2], interleukin 6 [IL-6] and tumor necrosis factor a [TNFa]; nitric oxide) and cytotoxicity (MTT-test and DNA content analysis) in mouse RAW264.7 macrophage cell line. At least the 1.5-fold synergistic increase in cytokine production of RAW264.7 macrophages was detected when coexposure contained an equal amount or more fungal spores (S. chartarum) than bacterial spores (Str. californicus) compared to the sum response caused by these microbial spores separately.

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Murtoniemi T, Penttinen P, Nevalainen A, Hirvonen MR. Effects of microbial cocultivation on inflammatory and cytotoxic potential of spores. Inhal Toxicol. 2005 Nov;17(12):681-93. PMID: 16087574

In this study we have investigated the effects of cocultivation of certain indoor air microbes on the inflammatory and cytotoxic potential of their spores. We grew various microbial combinations made from strains of Streptomyces californicus, Stachybotrys chartarum, Aspergillus versicolor, and Penicillium spinulosum on wetted plasterboard. After 5 or 10 wk of growth, the spores were collected from the plasterboards, mouse RAW264.7 macrophages were exposed to the spores, and after 24 h the induced inflammatory and cytotoxic responses were analyzed. Among all the tested microbes and their combinations, the spores of Str. californicus proved to be the most potent inducer of cytotoxicity and inflammatory responses. These results indicate also that microbial coculture may support the growth of certain microbes with high immunotoxic potency such as Str.californicus. Furthermore, coculture containing S. chartarum and A. versicolor caused a synergistic increase in cytotoxicity compared to the sum response induced by the pure cultures, but no effect on inflammatory responses was detected. Generally, spore-induced cytotoxicity and production of inflammatory markers increased during the growth period from 5 to 10 wk, suggesting that the immunotoxic potency of spores increases with time.

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Huttunen Kati, Pelkonen Jukka, Nielsen Kristian Fogg F., Nuutinen Ulla, Jussila Juha, Hirvonen Maija-Riitta R.. Synergistic interaction in simultaneous exposure to Streptomyces californicus and Stachybotrys chartarum. Environmental health perspectives. 2004;112:659–665. PMID: 15121507

In this study, we investigated the inflammatory responses of mouse RAW264.7 macrophages after exposure to six indoor air microbes (Aspergillus versicolor, Penicillium spinulosum, Stachybotrys chartarum, Bacillus cereus, Mycobacterium terrae, and Pseudomonas fluorescens) alone and together with the actinomycete Streptomyces californicus. The production of nitric oxide, levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), and cytotoxicity were measured. The co-exposure to Sta. chartarum and Str. californicus caused a synergistic increase in the production of IL-6 but not other cytokines.Testing revealed a synergistic response in TNF-alpha and IL-6 production after coexposure to Str. californicus with both trichodermin and 7-alpha-hydroxytrichodermol. Exposure to Str. californicus induced the binding of NF-kappa-B proteins to the NF-kappa-B consensus sequence as well as to the natural NF-kappa-B site of the IL-6 promoter.

 

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