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Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs
Authors:Daniela Jakš    ,Ida Ć  urtović  ,Domagoj Kifer,Dubravka Raš    ,Nevenka Kopjar,Vedran Micek,Maja Peraica,Maja Š  egvić   Klarić  
Affiliation:1.Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (D.J.); (I.Ć.); (D.K.);2.Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia; (D.R.); (N.K.); (V.M.); (M.P.)
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.
Keywords:Aspergilli series Versicolores   sterigmatocystin   5-methoxysterigmatocystin   intratarcheal instillation   genotoxicity   pro-inflammatory cytokines
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