Behroozikha M, Saidee M, Allameh A
Department of Biochemistry, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, Iran.
Cancer Lett. 1992 Sep 14;66(1):69-76. doi: 10.1016/0304-3835(92)90282-z.
The capability of the newborn rat liver to detoxify aflatoxin B1 (AFB1), a potent hepatocarcinogen is not well understood. Our present results show that immature rats are deficient in the hepatic key factors involved in biotransformation of AFB1. The activities of cytosolic glutathione S-transferases and microsomal cytochrome P-450 along with cellular glutathione (GSH) content show postnatal developmental changes. The ability of hepatic subcellular preparation from newborn rats to convert AFB1 to its reactive epoxide form, is reported for the first time in this communication. Epoxidation of [3H]AFB1 in the presence of liver microsomes from different age-groups as measured by its adduct formation to calf thymus DNA in vitro shows that newborn rats are capable of catalyzing only minimal AFB1-DNA binding compared with that of adults. Addition of cytosolic fraction of various age groups to the system suggests that young rats are less efficient in modulating the binding as compared with adults. The amount of AFB1-GSH conjugate formed is also significantly higher when adult GSH S-transferase is involved in the system. These observations show that immature liver is less efficient than a mature organ in handling a chemical carcinogen and the metabolism of AFB1 by neonatal liver differs from that in the adult.
新生大鼠肝脏对黄曲霉毒素B1（AFB1，一种强效肝致癌物）的解毒能力尚未得到充分了解。我们目前的结果表明，未成熟大鼠缺乏参与AFB1生物转化的肝脏关键因子。胞质谷胱甘肽S-转移酶和微粒体细胞色素P-450的活性以及细胞内谷胱甘肽（GSH）含量呈现出生后发育变化。本文首次报道了新生大鼠肝脏亚细胞制剂将AFB1转化为其活性环氧化物形式的能力。通过体外测量其与小牛胸腺DNA的加合物形成来检测不同年龄组肝脏微粒体存在下[3H]AFB1的环氧化，结果表明与成年大鼠相比，新生大鼠仅能催化极少的AFB1-DNA结合。向该系统中添加不同年龄组的胞质部分表明，与成年大鼠相比，幼鼠在调节结合方面效率较低。当成年谷胱甘肽S-转移酶参与该系统时，形成的AFB1-GSH缀合物的量也显著更高。这些观察结果表明，未成熟的肝脏在处理化学致癌物方面比成熟器官效率更低，并且新生肝脏对AFB1的代谢与成年肝脏不同。
