Cawood M E, Gelderblom W C, Alberts J F, Snyman S D
Program on Mycotoxins and Experimental Carcinogenesis, South African Medical Research Council, Tygerberg.
Food Chem Toxicol. 1994 Jul;32(7):627-32. doi: 10.1016/0278-6915(94)90006-x.
An in vitro study on the interaction and biotransformation of the [14C]fumonisin B mycotoxins was conducted, using primary rat hepatocyte cultures and subcellular enzyme preparations. At the same concentration, fumonisin B2 (FB2) exhibited a higher cytotoxicity and specific binding to primary rat hepatocytes than fumonisin B1 (FB1). However, if the effective dose level (EDL) is considered (i.e. the lowest level of toxin that binds to the hepatocytes to elicit a cytotoxic effect), FB1 and FB2 exhibited a similar cytotoxic effect. FB1 was found to be associated with both the soluble and insoluble compartments within the cell. As assessed by the radioactivity associated with the cellular preparations, very little (approximately 0.01%) FB1 and/or FB2 bound to hepatocytes. In the subsequent fractionation of the culture medium using amberlite XAD-2 and silica-gel chromatography, no metabolites were detected, indicating that the fumonisin molecule was not metabolized by primary hepatocytes. The latter aspect was confirmed by the fact that incubation of FB1 with microsomal enzyme preparations also failed to indicate any metabolism of the fumonisins by the esterases or by cytochrome P-450 monooxygenase. FB1 was also found not to be a substrate for the triglyceride hepatic endothelial lipase, nor for a lipase from porcine pancreas. This study supports further the hypothesis that the intact molecule of the fumonisins is required for biological activity.
利用原代大鼠肝细胞培养物和亚细胞酶制剂，对[14C]伏马菌素B霉菌毒素的相互作用和生物转化进行了一项体外研究。在相同浓度下，伏马菌素B2（FB2）对原代大鼠肝细胞的细胞毒性和特异性结合高于伏马菌素B1（FB1）。然而，如果考虑有效剂量水平（EDL）（即与肝细胞结合以引发细胞毒性作用的最低毒素水平），FB1和FB2表现出相似的细胞毒性作用。发现FB1与细胞内的可溶性和不可溶性部分均有关联。通过与细胞制剂相关的放射性评估，与肝细胞结合的FB1和/或FB2极少（约0.01%）。在随后使用Amberlite XAD - 2和硅胶色谱法对培养基进行分级分离时，未检测到代谢产物，这表明伏马菌素分子未被原代肝细胞代谢。FB1与微粒体酶制剂孵育也未能表明酯酶或细胞色素P - 450单加氧酶对伏马菌素的任何代谢，这一事实证实了后一方面。还发现FB1既不是肝内皮甘油三酯脂肪酶的底物，也不是猪胰腺脂肪酶的底物。这项研究进一步支持了这样的假设，即伏马菌素的完整分子对于生物活性是必需的。
