Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, València, Spain.
Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, València, Spain.
Food Chem Toxicol. 2018 Aug;118:719-725. doi: 10.1016/j.fct.2018.06.024. Epub 2018 Jun 15.
Mycotoxins are produced by a number of fungal genera spp as e.g. Aspergillus, Penicillium, Alternaria, Fusarium and Claviceps. 3-Acetyl-Deoxynivalenol (3-A-DON) and 15-Acetyl-Deoxynivalenol (15-ADON) which are produced by Fusarium, chemically belong to trichothecenes and occur in significant amounts as modified forms of deoxynivalenol (DON) in various cereal crops and processed grains. This study aims to determine the cytotoxicity, cell cycle and genotoxicity of the mycotoxins DON, 3-A-DON and 15-A-DON on HepG2 cells. Cytotoxic concentration range studied was from 100 to 3.1 μM for DON and 12.5 to 0.04 μM for 3-A-DON and 15-A-DON by the Neutral Red (NR) assay, over 24, 48 and 72 h. Potential of toxicity of 3-ADON in HepG2 cells was the highest at all times assayed. Cell cycle arrest in G0/G1 and G2/M phase was detected for all mycotoxins either in individually or in combined treatment in HepG2 cells. Genotoxicity was performed through micronuclei (MN) induction (TG 487) revealing significant effects for 3-ADON mycotoxin and in several combinations. It was evidenced that cell cycle alterations detected were associated to MN induction at all doses assayed, reaching the highest induction in tertiary combinations and in the binary combination 3-ADON + 15-ADON.
真菌的一些属种如曲霉属、青霉属、交链孢属、镰刀菌属和麦角菌属等都会产生霉菌毒素。3-乙酰脱氧雪腐镰刀菌烯醇（3-乙酰-DON）和 15-乙酰脱氧雪腐镰刀菌烯醇（15-乙酰-DON）是镰刀菌产生的，化学上属于单端孢霉烯族化合物，以脱氧雪腐镰刀菌烯醇（DON）的修饰形式大量存在于各种谷物作物和加工谷物中。本研究旨在确定霉菌毒素 DON、3-乙酰-DON 和 15-乙酰-DON 对 HepG2 细胞的细胞毒性、细胞周期和遗传毒性。通过中性红（NR）测定法，在 24、48 和 72 h 时，研究了 DON 的细胞毒性浓度范围为 100 至 3.1 μM，3-乙酰-DON 和 15-乙酰-DON 的浓度范围为 12.5 至 0.04 μM。在所有测定时间内，3-乙酰-DON 在 HepG2 细胞中的毒性潜力均最高。在 HepG2 细胞中，所有霉菌毒素单独或联合处理均检测到细胞周期阻滞在 G0/G1 和 G2/M 期。通过微核（MN）诱导（TG 487）进行遗传毒性检测，结果显示 3-乙酰-DON 霉菌毒素及其多种组合均具有显著的遗传毒性作用。结果表明，在所有测定剂量下，检测到的细胞周期改变与 MN 诱导有关，在三级组合和二元组合 3-乙酰-DON+15-乙酰-DON 中诱导率最高。
