Rahimtula A D, Martin M
Chem Biol Interact. 1984 Feb;48(2):207-20. doi: 10.1016/0009-2797(84)90122-4.
Administration of the phenolic antioxidant 2(3)-t-butyl-4-hydroxyanisole (BHA) to mice resulted in a 2-3-fold increase in the liver microsome catalyzed irreversible binding of aflatoxin B1 (AFB1) to calf thymus DNA and up to a 5-fold increase in the ability to induce mutations in Salmonella typhimurium TA98. Maximum induction of AFB1 binding to DNA occurred after 2 days of BHA administration whereas cytosolic glutathione S-transferase was maximally induced (6-fold) only after 10 days of BHA feeding. The induction of a new cytochrome P-450 species was indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and an enhanced sensitivity to inhibition by metyrapone and alpha-naphthoflavone. Addition of control cytosol (containing glutathione S-transferase) + glutathione to control microsomes decreased AFB1 binding to DNA by 26%. However, replacement of control cytosol by BHA cytosol which contained 6 times more glutathione S-transferase only marginally enhanced the inhibition to 38%. These data suggest that BHA may exert its effect in the liver primarily through an alteration of the cytochrome P-450 dependent activation process although an increase in the conjugation of reactive metabolite may play a contributory role.
给小鼠施用酚类抗氧化剂2(3)-叔丁基-4-羟基茴香醚（BHA）后，肝脏微粒体催化黄曲霉毒素B1（AFB1）与小牛胸腺DNA的不可逆结合增加了2至3倍，在鼠伤寒沙门氏菌TA98中诱导突变的能力增加了高达5倍。BHA给药2天后，AFB1与DNA的结合诱导达到最大值，而胞质谷胱甘肽S-转移酶仅在BHA喂养10天后才被最大程度诱导（6倍）。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）表明诱导了一种新的细胞色素P-450种类，并且对甲吡酮和α-萘黄酮抑制的敏感性增强。向对照微粒体中添加对照胞质溶胶（含有谷胱甘肽S-转移酶）+谷胱甘肽可使AFB1与DNA的结合减少26%。然而，用谷胱甘肽S-转移酶含量高6倍的BHA胞质溶胶替代对照胞质溶胶，仅将抑制作用略微增强至38%。这些数据表明，BHA可能主要通过改变细胞色素P-450依赖性激活过程在肝脏中发挥作用，尽管反应性代谢物结合的增加可能起辅助作用。
