Saxena M, Allameh A, Mukerji K G, Raj H G
Department of Biochemistry, Vallabhbhai Patel Chest Institute, Delhi, India.
Chem Biol Interact. 1991;78(1):13-22. doi: 10.1016/0009-2797(91)90099-s.
Metabolism of aflatoxin B1 (AFB1) by subcellular preparations of Aspergillus flavus is least understood. The results reported here have demonstrated for the first time the epoxidation of AFB1 and subsequent conjugation with glutathione (GSH). Microsomes prepared from toxigenic mycelia catalysed [3H]AFB1 to calf thymus DNA to a greater extent (approximately 2-fold) as compared to that of non-toxigenic. The binding of [3H]AFB1 to exogenous and A. flavus nuclear DNA catalyzed by A. flavus microsomes was found to be comparable with that of mammalian extrahepatic tissue such as lung. Addition of phenobarbitone to the growing cultures resulted in 1.5-fold increase in [3H]AFB1-DNA binding mediated by microsomes prepared from either of the two strains. Tolnaftate, an inhibitor of aflatoxin synthesis enhanced the epoxidation rate in a dose-related manner. The binding of [3H]AFB1 to DNA catalyzed by A. flavus microsomes was significantly reduced (50% of control) upon addition of hamster liver cytosol, thereby substantiating the formation of the carcinogen adduct with DNA as reported in mammalian tissues. The metabolite formed by subcellular preparation of A. flavus was found to be AFB1-GSH having Rf value (6.5) similar to that obtained for mammalian liver preparations.
黄曲霉亚细胞制剂对黄曲霉毒素B1（AFB1）的代谢了解最少。此处报道的结果首次证明了AFB1的环氧化以及随后与谷胱甘肽（GSH）的结合。与非产毒菌丝体制备的微粒体相比，产毒菌丝体制备的微粒体催化[3H]AFB1与小牛胸腺DNA的结合程度更高（约2倍）。发现黄曲霉微粒体催化的[3H]AFB1与外源和黄曲霉核DNA的结合与哺乳动物肝外组织如肺的结合相当。向生长的培养物中添加苯巴比妥导致由两种菌株之一制备的微粒体介导的[3H]AFB1-DNA结合增加1.5倍。托萘酯，一种黄曲霉毒素合成抑制剂，以剂量相关的方式提高环氧化速率。添加仓鼠肝细胞溶胶后，黄曲霉微粒体催化的[3H]AFB1与DNA的结合显著降低（对照的50%），从而证实了如在哺乳动物组织中报道的致癌物加合物与DNA的形成。发现黄曲霉亚细胞制剂形成的代谢产物是AFB1-GSH，其Rf值（6.5）与哺乳动物肝脏制剂获得的Rf值相似。
