Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia.
Toxins (Basel). 2020 Nov 23;12(11):734. doi: 10.3390/toxins12110734.
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series . 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.
表型霉素(STC)和 5-甲氧基表型霉素(5-M-STC)是由常见的室内曲霉菌系列产生的真菌毒素。由于 STC 和 5-M-STC 都在室内职业和生活区域的灰尘中被发现,其居住者可能会通过吸入的方式暴露于这些真菌毒素。因此,使用相当于室内潮湿环境灰尘中检测到的浓度的剂量(0.3mg STC/kg 肺重(l.w.);3.6mg 5-M-STC/kg l.w.;毒素组合 0.3+3.6mg/kg l.w.),通过气管内滴注将 STC 和 5-M-STC 注入雄性 Wistar 大鼠体内,以探索细胞毒性、血管通透性、免疫调节和遗传毒性。单一真菌毒素及其组合对 24 小时处理后支气管肺泡灌洗液中的乳酸脱氢酶活性、白蛋白、白细胞介素-6、肿瘤坏死因子-α和趋化因子巨噬细胞炎性蛋白-1α浓度的影响,通过 ELISA 进行了测量,没有明显变化。在碱性彗星试验中,两种真菌毒素在大鼠肺部均引起类似强度的 DNA 损伤,而在中性彗星试验中,只有 5-M-STC 引起明显的 DNA 损伤。因此,自然存在的 STC 浓度可能会在大鼠肺部引起 DNA 损伤,其中单链 DNA 断裂占主导地位,而 5-M-STC 则更易导致双链断裂。在彗星试验的两种版本中,与单一真菌毒素处理相比,STC+5-M-STC 处理导致的 DNA 损伤强度较低,表明存在拮抗遗传毒性作用。