Zheng G Q, Kenney P M, Lam L K
LKT Laboratories Inc., Minneapolis, MN 55413.
J Pharm Sci. 1992 Sep;81(9):950-3. doi: 10.1002/jps.2600810923.
Two nitroaromatic compounds, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4-dinitrobenzene (1) and 1-[4-(1,1-dimethylethyl)-2,6-dimethyl-3,5-dinitrophenyl]ethanone or musk ketone (2), were isolated from ambrette musk residue, which is widely used in the food and cosmetics industry. The ability of 1 and 2 to induce increased activity of the detoxifying enzyme glutathione S-transferase was tested in A/J mice. Enzyme induction in the cytosols of liver, forestomach, lung, colon, and small intestinal mucosa was determined. Biological evaluation revealed that both compounds exhibit high activity as glutathione S-transferase inducers in liver and small intestinal mucosa. The effects of 1 and 2 on the levels of acid-soluble sulfhydryl in the five mouse tissues were also determined. Both compounds slightly elevated sulfhydryl levels in the small intestinal mucosa but significantly decreased the sulfhydryl levels in the other tissues. Because the ability of anticarcinogenic compounds to induce an increase in the detoxifying enzyme activity correlates with their tumor inhibitory activity, 1 and 2 may be potential cancer chemopreventive agents.
从广泛应用于食品和化妆品行业的黄葵麝香残渣中分离出两种硝基芳香族化合物，1-(1,1-二甲基乙基)-3,5-二甲基-2,4-二硝基苯(1)和1-[4-(1,1-二甲基乙基)-2,6-二甲基-3,5-二硝基苯基]乙酮即麝香酮(2)。在A/J小鼠中测试了化合物1和2诱导解毒酶谷胱甘肽S-转移酶活性增加的能力。测定了肝脏、前胃、肺、结肠和小肠黏膜胞质溶胶中的酶诱导情况。生物学评价显示，这两种化合物在肝脏和小肠黏膜中均表现出作为谷胱甘肽S-转移酶诱导剂的高活性。还测定了化合物1和2对五种小鼠组织中酸溶性巯基水平的影响。两种化合物均使小肠黏膜中的巯基水平略有升高，但使其他组织中的巯基水平显著降低。由于抗癌化合物诱导解毒酶活性增加的能力与其肿瘤抑制活性相关，因此化合物1和2可能是潜在的癌症化学预防剂。
