Sawada Stefanie, Oberemm Axel, Buhrke Thorsten, Meckert Christine, Rozycki Christel, Braeuning Albert, Lampen Alfonso
Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
Food Chem Toxicol. 2015 Sep;83:84-92. doi: 10.1016/j.fct.2015.06.002. Epub 2015 Jun 11.
Thermal treatment of foodstuff containing fats and salt promotes the formation of 3-chloropropane-1,2-diol (3-MCPD) and its fatty acid esters. 3-MCPD-exposed rats develop testicular lesions and Leydig cell tumors. 3-MCPD and 3-MCPD ester toxicity is thought to be caused by 3-MCPD and its metabolites, since 3-MCPD esters are hydrolyzed in the gut. Inhibition of glycolysis is one of the few known molecular mechanisms of 3-MCPD toxicity. To obtain deeper insight into this process, a comparative proteomic approach was chosen, based on a 28-days repeated-dose feeding study with male Wistar rats. Animals received equimolar doses of 3-MCPD or 3-MCPD dipalmitate. A lower dose of 3-MCPD dipalmitate was also administered. Absence of histopathological changes supported an analysis of early cellular disturbance. Testes were analyzed by two-dimensional gel electrophoresis followed by mass-spectrometric protein identification. Data provide a comprehensive overview of proteomic changes induced by 3-MCPD and 3-MCPD dipalmitate in rat testis in an early phase of organ impairment. Results are compatible with known 3-MCPD effects on reproductive function, substantially extend our knowledge about cellular responses to 3-MCPD and support the hypothesis that toxicity of 3-MCPD and 3-MCPD esters is mediated via common effectors. DJ-1 was identified as a candidate marker for 3-MCPD exposure.
对含有脂肪和盐分的食品进行热处理会促进3-氯-1,2-丙二醇(3-MCPD)及其脂肪酸酯的形成。接触3-MCPD的大鼠会出现睾丸损伤和睾丸间质细胞瘤。3-MCPD及其酯类的毒性被认为是由3-MCPD及其代谢产物引起的,因为3-MCPD酯类在肠道中会水解。抑制糖酵解是3-MCPD毒性为数不多的已知分子机制之一。为了更深入地了解这一过程,基于对雄性Wistar大鼠进行的为期28天的重复剂量喂养研究,选择了一种比较蛋白质组学方法。动物接受等摩尔剂量的3-MCPD或3-MCPD二棕榈酸酯。还给予了较低剂量的3-MCPD二棕榈酸酯。组织病理学变化的缺失支持了对早期细胞紊乱的分析。通过二维凝胶电泳分析睾丸,随后进行质谱蛋白质鉴定。数据全面概述了在器官损伤早期3-MCPD和3-MCPD二棕榈酸酯在大鼠睾丸中诱导的蛋白质组变化。结果与已知的3-MCPD对生殖功能的影响相符,极大地扩展了我们对细胞对3-MCPD反应的认识,并支持了3-MCPD及其酯类毒性是通过共同效应器介导的这一假说。DJ-1被鉴定为3-MCPD暴露的候选标志物。