Shikhaliyeva Inji, Kığ Cenk, Gömeç Ömer Yavuz, Albayrak Gülruh
İstanbul University, Institute of Graduate Studies in Sciences, Programme of Molecular Biology and Genetics, İstanbul, Türkiye.
İstanbul University, Faculty of Sciences, Department of Molecular Biology and Genetics, İstanbul, Türkiye.
Turk J Pharm Sci. 2024 Mar 25;21(1):62-70. doi: 10.4274/tjps.galenos.2023.76128.
Humans are unknowingly exposed to mycotoxins through the consumption of plant-derived foods and processed products contaminated with these toxic compounds. In addition to agricultural losses, Fusarium toxins pose a threat to human health. However, the effects of fusariotoxins on the viability and proliferation of stem cells have not been fully explored. We investigated the cytotoxic effects of deoxynivalenol (DON) and B-trichothecene mix (MIX) on mesenchymal stem cells (MSCs) and the L929 fibroblast cell line.
MSCs were isolated from the dental pulp tissue. The doubling time and viability of dental pulp stem cells (DPSCs) and L929 cells were determined using the MTT assay. The following doses of B-trichothecenes (0.25-16 µg/mL; 24 hours and 48 hours) were used to evaluate cytotoxicity. In addition, changes in the confluency-dependent response of DPSCs to DON toxicity were determined. Moreover, we investigated the effect of DON on cell death acridine orange/ethidium bromide (AO/EB) double staining.
A DON and MIX showed a dose- and time-dependent inhibitory effect on the proliferation of both cells. DPSCs exposed to DON for 48 hours (IC = 0.5 μg/mL) were found to be 16-fold more sensitive than L929 cells (IC = 8 μg/mL). Compared with a culture with 80% confluency, DPSCs from a 50% confluent culture were more sensitive to varying doses of DON (0.25-4 µg/mL, 24-48 hours). Moreover, AO/EB staining showed that treatment of DPSCs with DON led to a significant increase in cell death (17% for 2.4 µg/mL; 50% for 4.8 µg/mL).
This study reveals that undifferentiated MSCs are significantly more sensitive to DON than differentiated somatic cells (L929). Given that humans are frequently exposed to these mycotoxins, our findings imply that prolonged exposure to them may also have harmful effects on cellular differentiation and embryonic development.
人类在不知不觉中通过食用受这些有毒化合物污染的植物性食品和加工产品而接触到霉菌毒素。除了造成农业损失外，镰刀菌毒素还对人类健康构成威胁。然而，镰刀菌毒素对干细胞活力和增殖的影响尚未得到充分研究。我们研究了脱氧雪腐镰刀菌烯醇（DON）和B-单端孢霉烯混合物（MIX）对间充质干细胞（MSCs）和L929成纤维细胞系的细胞毒性作用。
从牙髓组织中分离出MSCs。使用MTT法测定牙髓干细胞（DPSCs）和L929细胞的倍增时间和活力。使用以下剂量的B-单端孢霉烯（0.25 - 16μg/mL；24小时和48小时）来评估细胞毒性。此外，还确定了DPSCs对DON毒性的汇合依赖性反应的变化。此外，我们研究了DON对吖啶橙/溴化乙锭（AO/EB）双重染色的细胞死亡的影响。
DON和MIX对两种细胞的增殖均表现出剂量和时间依赖性抑制作用。发现暴露于DON 48小时（IC = 0.5μg/mL）的DPSCs比L929细胞（IC = 8μg/mL）敏感16倍。与80%汇合度的培养物相比，50%汇合度培养物中的DPSCs对不同剂量的DON（0.25 - 4μg/mL，24 - 48小时）更敏感。此外，AO/EB染色显示，用DON处理DPSCs导致细胞死亡显著增加（2.4μg/mL时为17%；4.8μg/mL时为50%）。
本研究表明，未分化的MSCs对DON的敏感性明显高于分化的体细胞（L929）。鉴于人类经常接触这些霉菌毒素，我们的研究结果表明，长期接触它们可能也会对细胞分化和胚胎发育产生有害影响。
