Ch'ih J J, Biedrzycka D W, Devlin T M
Department of Biological Chemistry, Hahnemann University School of Medicine, Philadelphia, PA 19102.
Biochem Biophys Res Commun. 1991 Aug 15;178(3):1002-7. doi: 10.1016/0006-291x(91)90991-f.
The intra- and extra-cellular concentrations of AFB1, AFM1, AFP1, AFQ1 and their conjugates were quantitatively determined after 60 min of incubation with [3H]-AFB1 (1500 pmol/10(8) cells). Comparing the total concentrations of water-soluble conjugates, the eight fold greater amounts found in the medium (718 pmol) than in the cell (86 pmol) indicate that these detoxication products were excreted soon after they were formed. When the cells were perturbed with butylated hydroxyanisole (BHA), a noncompetitive inhibitor of the mixed-function oxidases, accumulations of intracellular AFB1 and extracellular AFB1 were observed. In a cell-free microsomal system, the AFB1 was metabolized at a slower rate than in intact cells. When the activation of AFB1 is blocked, the accumulation of intracellular AFB1 and decreased internalization of AFB1 suggest that AFB1 uptake, translocation of AFB1 from site of entry to site of actions, oxidation by cytochrome P-450-dependent monoxygenase, metabolic detoxication and conjugation reactions, and excretion of water soluble metabolites are linked.
用[³H]-黄曲霉毒素B1（1500皮摩尔/10⁸个细胞）孵育60分钟后，对黄曲霉毒素B1、黄曲霉毒素M1、黄曲霉毒素P1、黄曲霉毒素Q1及其共轭物的细胞内和细胞外浓度进行了定量测定。比较水溶性共轭物的总浓度，培养基中发现的量（718皮摩尔）比细胞中发现的量（86皮摩尔）多八倍，这表明这些解毒产物在形成后很快就被排泄了。当用丁基羟基茴香醚（BHA）（一种混合功能氧化酶的非竞争性抑制剂）干扰细胞时，观察到细胞内黄曲霉毒素B1和细胞外黄曲霉毒素B1的积累。在无细胞微粒体系统中，黄曲霉毒素B1的代谢速度比完整细胞中慢。当黄曲霉毒素B1的活化被阻断时，细胞内黄曲霉毒素B1的积累和黄曲霉毒素B1内化的减少表明，黄曲霉毒素B1的摄取、从进入部位到作用部位的转运、细胞色素P-450依赖性单加氧酶的氧化、代谢解毒和共轭反应以及水溶性代谢产物的排泄是相互关联的。
