Thapliyal R, Deshpande S S, Maru G B
Carcinogenesis Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai, India.
J Environ Pathol Toxicol Oncol. 2001;20(1):59-63.
Turmeric and/or its main coloring component, curcumin (diferuloylmethane), have been shown to inhibit benzo(a)pyrene [B(a)P]-induced forestomach papillomas in mice. However, the mechanisms of turmeric-mediated chemoprevention are not well understood. To study the mechanisms of turmeric-mediated chemoprevention, we investigated the effects of turmeric feeding on the activities of isozymes of cytochrome P-450 (CYP450)--namely, ethoxyresorufin O-deethylase (EROD, CYP1A1) and methoxyresorufin O-demethylase (MROD, CYP1A2)--which are predominantly involved in the metabolism of B(a)P. We determined the activities of EROD and MROD by monitoring the formation of resorufin from respective substrates in the presence of microsomal proteins obtained from tissues of control, 1% turmeric, 1 mg B(a)P, and 1% turmeric + 1 mg B(a)P-fed Swiss mice. The results indicate that the administration of turmeric through diet significantly inhibited the activities of both EROD and MROD in forestomach (target organ), liver, and lung. In vitro studies employing curcumin, demethoxycurcumin, and bis-demethoxycurcumin suggest that curcumins are the inhibitors in turmeric. Inhibition of B(a)P metabolizing phase I enzymes (EROD, MROD) may be at least in part one of the possible modes of chemopreventive action of turmeric/curcumin.
姜黄和/或其主要色素成分姜黄素（双阿魏酰甲烷）已被证明可抑制苯并(a)芘[B(a)P]诱导的小鼠前胃乳头瘤。然而，姜黄介导的化学预防机制尚不清楚。为了研究姜黄介导的化学预防机制，我们研究了喂食姜黄对细胞色素P-450（CYP450）同工酶活性的影响，即乙氧异吩唑酮O-脱乙基酶（EROD，CYP1A1）和甲氧基异吩唑酮O-脱甲基酶（MROD，CYP1A2），它们主要参与B(a)P的代谢。我们通过监测在从对照、1%姜黄、1mg B(a)P和1%姜黄+1mg B(a)P喂养的瑞士小鼠组织中获得的微粒体蛋白存在下，从各自底物形成试卤灵的情况，来测定EROD和MROD的活性。结果表明，通过饮食给予姜黄可显著抑制前胃（靶器官）、肝脏和肺中EROD和MROD的活性。使用姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素的体外研究表明，姜黄素类是姜黄中的抑制剂。抑制B(a)P代谢的I相酶（EROD、MROD）可能至少部分是姜黄/姜黄素化学预防作用的可能模式之一。
