Laboratoire de Toxicologie Alimentaire et Cellulaire, Université Européenne de Bretagne-Université de Bretagne Occidentale (UEB-UBO), 6 Av. Victor Le Gorgeu, CS93837, 29238 Brest Cedex 3, France.
Toxicon. 2012 Jan;59(1):182-91. doi: 10.1016/j.toxicon.2011.11.006. Epub 2011 Nov 19.
The aim of this study was to screen potential myelotoxicity of the emerging mycotoxins Beauvericin, Enniatin b and Moniliformin using human hematopoietic progenitor clonogenic assays. Depending on mycotoxins, inhibitory effects on proliferation of white blood cells progenitors (CFU-GM), platelet progenitors (CFU-MK) and red blood cells progenitors (BFU-E) have been detected at various concentrations. Beauvericin was cytotoxic at 32μM, 3.2μM and 6.4μM, had no effect on proliferation in the presence of 0.032μM, 0.16μM and 0.064μM, and the IC(50) was equal to 3.4μM, 0.7μM and 3.7μM for CFU-GM, CFU-MK and BFU-E, respectively. Enniatin b was cytotoxic at 6μM, 1.8μM and 5μM, had no effect on proliferation in the presence of 1μM, 1.1μM and 1.2μM and the IC(50) was equal to 4.4μM, 1.3μM and 3.3μM for CFU-GM, CFU-MK and BFU-E, respectively. Moniliformin was not cytotoxic at tested concentrations for CFU-GM and CFU-MK and cytotoxic at 10μM for BFU-E, had no effect on proliferation in the presence of 5μM, 0.1μM and 0.1μM and the IC(50) was equal to 31μM, 39μM and 4.1μM for CFU-GM, CFU-MK and BFU-E, respectively. Inhibition of the BFU-E differentiation has been observed in the presence of Enniatin b or Moniliformin. For the three mycotoxins, variation of distribution of CFU-MK colonies according to their size has been observed. These in vitro effects may be responsible for in vivo hematological troubles in case of consumption of contaminated commodities. In vivo studies have to be performed to test this hypothesis.
本研究旨在使用人类造血祖细胞集落形成测定法筛选新兴霉菌毒素伏马菌素 B1、恩镰孢菌素 B 和单端孢霉烯族化合物的潜在骨髓毒性。根据霉菌毒素的不同,在各种浓度下已经检测到对白血细胞祖细胞 (CFU-GM)、血小板祖细胞 (CFU-MK) 和红血细胞祖细胞 (BFU-E) 的增殖有抑制作用。伏马菌素 B1 在 32μM、3.2μM 和 6.4μM 时具有细胞毒性,在 0.032μM、0.16μM 和 0.064μM 时对增殖没有影响,其 IC50 分别为 3.4μM、0.7μM 和 3.7μM,用于 CFU-GM、CFU-MK 和 BFU-E。恩镰孢菌素 B 在 6μM、1.8μM 和 5μM 时具有细胞毒性,在 1μM、1.1μM 和 1.2μM 时对增殖没有影响,其 IC50 分别为 4.4μM、1.3μM 和 3.3μM,用于 CFU-GM、CFU-MK 和 BFU-E。单端孢霉烯族化合物在测试浓度下对 CFU-GM 和 CFU-MK 无细胞毒性,对 BFU-E 有细胞毒性,在 5μM、0.1μM 和 0.1μM 时对增殖没有影响,其 IC50 分别为 31μM、39μM 和 4.1μM,用于 CFU-GM、CFU-MK 和 BFU-E。在恩镰孢菌素 B 或单端孢霉烯族化合物存在下观察到 BFU-E 分化的抑制。对于三种霉菌毒素,已经观察到 CFU-MK 集落根据其大小分布的变化。这些体外效应可能是摄入受污染商品后体内血液学问题的原因。必须进行体内研究来验证这一假设。