Moreno Fernando Salvador, Toledo Luciana Passos, de Conti Aline, Heidor Renato, Jordão Alceu, Vannucchi Hélio, Cardozo Mônica Testoni, Ong Thomas Prates
Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes 580, Bloco 14, 05508-900 São Paulo, SP, Brazil.
Chem Biol Interact. 2007 Jul 20;168(3):221-8. doi: 10.1016/j.cbi.2007.04.011. Epub 2007 May 4.
Cancer chemopreventive agents are classified as blocking or suppressing agents if they inhibit initiation or promotion/progression phase of carcinogenesis, respectively. Two experiments were conducted in order to classify lutein as a blocking and/or suppressing agent during rat hepatocarcinogenesis. Inhibitory effects of lutein on hepatic preneoplastic lesions (PNL) and DNA strand breakage induced in Wistar rats by the resistant hepatocyte model of hepatocarcinogenesis (initiation with diethylnitrosamine and promotion with 2-acetylaminofluorene coupled with partial hepatectomy) were investigated when the carotenoid was administered specifically during initiation (experiment 1) or promotion (experiment 2) phase. Animals received by gavage during 2 (experiment 1) or six (experiment 2) consecutive weeks on alternate days 70 mg/kg body weight of lutein. Rats treated with only corn oil during these same periods and submitted to this model were used as controls. Treatment with lutein during initiation did not inhibit nor induced (P>0.05) hepatic preneoplastic lesions and DNA damage. On the other hand, treatment during promotion inhibited (P<0.05) the size of hepatic macroscopic nodules and DNA damage and increased (P<0.05) lutein hepatic levels that reached levels seen in human liver samples. Lutein presented inhibitory actions during promotion but not initiation of hepatocarcinogenesis, being classified as a suppressing agent. This reinforces lutein as a potential agent for liver cancer chemoprevention.
癌症化学预防剂如果分别抑制致癌作用的起始或促进/进展阶段,则被分类为阻断剂或抑制剂。进行了两项实验,以将叶黄素分类为大鼠肝癌发生过程中的阻断剂和/或抑制剂。当在起始阶段(实验1)或促进阶段(实验2)特异性给予类胡萝卜素时,研究了叶黄素对Wistar大鼠肝癌发生的抗性肝细胞模型(用二乙基亚硝胺起始并用2-乙酰氨基芴促进并结合部分肝切除术)诱导的肝前体病变(PNL)和DNA链断裂的抑制作用。动物在连续2周(实验1)或6周(实验2)内隔天经口灌胃给予70mg/kg体重的叶黄素。在相同时间段内仅用玉米油处理并采用该模型的大鼠用作对照。在起始阶段给予叶黄素治疗既不抑制也不诱导(P>0.05)肝前体病变和DNA损伤。另一方面,在促进阶段给予治疗可抑制(P<0.05)肝大体结节的大小和DNA损伤,并增加(P<0.05)叶黄素肝脏水平,达到人肝脏样本中的水平。叶黄素在肝癌发生的促进阶段而非起始阶段呈现抑制作用,被分类为抑制剂。这进一步证明叶黄素是一种潜在的肝癌化学预防剂。