Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout.
Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout.
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膳食植物化学物质 3,3-二吲哚基甲烷在虹鳟鱼中增强肿瘤过程中的基因表达分析。
DOI：
10.1093/carcin/bgm017
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发表时间：
2007
期刊：
影响因子：
4.7
通讯作者：
Williams,DavidE
中科院分区：
文献类型：
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作者：
Tilton,SusanC;Hendricks,JerryD;Orner,GayleA;Pereira,CliffB;Bailey,GeorgeS;Williams,DavidE
吲哚-3-甲醇（I3 C）和3，3 ′-二吲哚基甲烷（DIM）是一种主要的I3 C衍生物，是已知的膳食化学预防剂，也可作为补充剂使用。然而，已发现I3 C在大鼠（多器官）和鳟鱼（肝脏）模型中充当肿瘤促进剂。I3 C和DIM先前被发现是雌激素在鳟鱼肝脏的基础上毒理基因组学档案。在这项研究中，我们比较了DIM和17β-雌二醇（E2）对黄曲霉毒素B1（AFB 1）诱导的鳟鱼肝癌发生的后启动效应。以黄曲霉毒素B_1作为胚胎，幼鱼分别饲喂含0、120或400 p. p. m. DIM或5 p.p.m.E_2的饲料18周。在13个月时确定肿瘤发病率，发现与对照组动物相比，AFB 1引发的鳟鱼喂食400 p. p.m. DIM或5 p. p.m. E2显著升高。为了评估肿瘤增强的机制，在肿瘤发生过程中和启动动物的肝细胞癌（HCC）中检查了喂食促进饮食的动物的肝脏基因表达谱。我们证明，DIM改变基因表达谱类似于E2在肝脏样本中的肿瘤发生过程中，在肝癌肿瘤。此外，与来自对照动物的HCC相比，来自DIM和E2促进饮食的动物的HCC具有指示降低的侵袭或转移潜力的转录特征。总的来说，这些发现是第一个证明肿瘤促进DIM。他们证实了雌激素信号的重要性，促进鳟鱼肝脏中的饮食吲哚的机制，并表明可能的双重作用，提高肿瘤发病率和降低转移的可能性。
Indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM), a primary I3C derivative, are known dietary chemopreventive agents also available as supplements. However, I3C has been found to act as a tumor promoter in rat (multi-organ) and trout (liver) models. I3C and DIM were previously found to be estrogenic in trout liver based on toxicogenomic profiles. In this study, we compare the post-initiation effects of DIM and 17β-estradiol (E2) on aflatoxin B1(AFB1)-induced hepatocarcinogenesis in trout. Trout were initiated as embryos with AFB1and juvenile fish were fed diets containing 0, 120 or 400 p.p.m. DIM or 5 p.p.m. E2 for 18 weeks. Tumor incidence was determined at 13 months and found to be significantly elevated in AFB1-initiated trout fed either 400 p.p.m. DIM or 5 p.p.m. E2 compared with control animals. To evaluate the mechanism of tumor enhancement, hepatic gene expression profiles were examined in animals fed promotional diets during the course of tumorigenesis and in hepatocellular carcinomas (HCCs) of initiated animals. We demonstrate that DIM alters gene expression profiles similar to E2 in liver samples during tumorigenesis and in HCC tumors. Further, HCCs from animals on DIM and E2 promotional diets had a transcriptional signature indicating decreased invasive or metastatic potential compared with HCCs from control animals. Overall, these findings are the first to demonstrate tumor promotion by DIM. They confirm the importance of estrogenic signaling in the mechanism of promotion by dietary indoles in trout liver and indicate a possible dual effect that enhances tumor incidence and decreases potential for metastasis.