Abstract
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series Versicolores. Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.
Highlights
Sterigmatocystin (STC) is one of the most commonly occurring polyketide mycotoxins in damp occupational and indoor living areas [1,2,3], principally produced by Aspergillus section Nidulantes seriesVersicolores that can be found in indoor damp occupational and living environments [4]
STC is activated by the liver cytochrome P450 (CYP450) system with reactive epoxide that forms DNA adducts with guanine, and this is considered the underlying mechanism of STC genotoxicity [9]
Our recent unpublished results revealed that STC (85%), along with its derivative 5-M-STC (70%), 3
Summary
Sterigmatocystin (STC) is one of the most commonly occurring polyketide mycotoxins in damp occupational and indoor living areas [1,2,3], principally produced by Aspergillus section Nidulantes series. Versicolores that can be found in indoor damp occupational and living environments [4]. Recent studies have shown that among Aspergilli series Versicolores, the most frequent contributors of STC in dust of occupational and/or residential environments were the species A. jensenii and A. creber, followed by. 5-Methoxysterigmatocystin (5-M-STC) is produced in association with STC by some. STC is activated by the liver cytochrome P450 (CYP450) system with reactive epoxide that forms DNA adducts with guanine, and this is considered the underlying mechanism of STC genotoxicity [9]. STC induces lung adenocarcinoma in mice, genotoxicity and G2 cell cycle arrest in human immortalized bronchial epithelial BEAS-2B cells, human lung adenocarcinoma A549 cells and human esophageal epithelial
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