Smith Marie-Caroline, Madec Stéphanie, Pawtowski Audrey, Coton Emmanuel, Hymery Nolwenn
Université de Brest, EA 3882, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, 29280 Plouzané, France.
Université de Brest, EA 3882, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, 29280 Plouzané, France.
Toxicol Lett. 2017 Oct 5;280:238-246. doi: 10.1016/j.toxlet.2017.08.080. Epub 2017 Sep 1.
While numerous surveys highlighted the natural co-occurrence of mycotoxins in food, data about their toxicological combined effects is still limited. This is especially the case for chronic exposure conditions, although the latter are more representative of the mycotoxin risk associated with food consumption than acute exposure. In the present study, cell viability and gene expression levels of relevant hepatocyte-specific functions were evaluated for the HepaRG human liver cell line exposed to deoxynivalenol (DON) and/or zearalenone (ZEA) during 14, 28 and 42days at three subtoxic concentrations corresponding to i) the determined average exposure dose of French adult population, ii) the tolerable daily intake established by the Joint FAO/WHO Expert Committee and iii) the maximum level permitted by the European regulation in cereals intended for direct human consumption. For the latter, DON and DON+ZEA induced 90% cell mortality after 14days. In addition, depending on the considered toxin or mixture, doses and exposure periods, important variations of gene expression levels were observed. Despite the fact that in vitro conditions differ from the in vivo situation, the obtained results clearly highlighted that long-term toxicological effects of chronic exposure to mycotoxin combinations should be further investigated and, if necessary, taken into consideration at the regulatory level.
尽管众多调查强调了食品中霉菌毒素的自然共存现象，但有关其毒理学联合效应的数据仍然有限。慢性暴露情况尤其如此，尽管后者比急性暴露更能代表与食品消费相关的霉菌毒素风险。在本研究中，对HepaRG人肝细胞系在14天、28天和42天内分别暴露于脱氧雪腐镰刀菌烯醇（DON）和/或玉米赤霉烯酮（ZEA）的三种亚毒性浓度下的细胞活力及相关肝细胞特异性功能的基因表达水平进行了评估，这三种浓度分别对应于：i）法国成年人群的确定平均暴露剂量；ii）联合国粮食及农业组织/世界卫生组织联合专家委员会确定的每日可耐受摄入量；iii）欧洲法规对供人类直接消费的谷物所允许的最高限量。对于后者，DON以及DON + ZEA在14天后诱导了90%的细胞死亡率。此外，根据所考虑的毒素或混合物、剂量和暴露时间的不同，观察到基因表达水平存在重要差异。尽管体外条件与体内情况不同，但所获得的结果清楚地表明，应进一步研究霉菌毒素组合慢性暴露的长期毒理学效应，如有必要，在监管层面也应予以考虑。
