Dashwood R H, Fong A T, Arbogast D N, Bjeldanes L F, Hendricks J D, Bailey G S
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822.
Cancer Res. 1994 Jul 1;54(13):3617-9.
The relative contribution of indole-3-carbinol (I3C) and its acid condensation products to the anticarcinogenic activity of this crucifer phytochemical has been studied using trout embryo microinjection. I3C was treated with 0.07 N HCl to give a reaction mixture (RXM) comprising < 0.5% parent compound and over 20 products, the most prevalent being the dimer 3,3'-diindolylmethane (I33') and a related cyclic trimer (CT). RXM, I33' or CT was injected into embryos with [3H]aflatoxin B1 (AFB1) and total embryonic DNA was isolated 1, 3, or 10 days postinjection. Compared with controls given AFB1 alone, I3C failed to inhibit carcinogen-DNA binding at any time point. In contrast I33', CT, and RXM inhibited AFB1-DNA binding by an average of 37, 51, and 65%, respectively. Coinjection of AFB1 and 350 microM I3C, RXM, or I33' into trout embryos reduced AFB1-induced hepatocarcinogenesis after 1 year from 43.4% in positive controls to 36.0, 12.2 (P < 0.05), and 24.6% (P < 0.05), respectively. No tumor data were obtained in the AFB1 plus CT group due to poor survival of the embryos posthatching. These results indicate that acid condensation products, not the parent compound, represent the anticarcinogenic species in trout and that their formation in the stomach is a likely prerequisite for I3C anticarcinogenesis.
利用虹鳟鱼胚胎显微注射技术，研究了吲哚 - 3 - 甲醇（I3C）及其酸性缩合产物对这种十字花科植物化学物抗癌活性的相对贡献。I3C 用 0.07 N 盐酸处理，得到一种反应混合物（RXM），其中母体化合物含量小于 0.5%，还有 20 多种产物，最主要的是二聚体 3,3'-二吲哚甲烷（I33'）和一种相关的环状三聚体（CT）。将 RXM、I33' 或 CT 与 [3H]黄曲霉毒素 B1（AFB1）一起注射到胚胎中，并在注射后 1、3 或 10 天分离总胚胎 DNA。与仅给予 AFB1 的对照组相比，I3C 在任何时间点都未能抑制致癌物 - DNA 结合。相比之下，I33'、CT 和 RXM 分别平均抑制 AFB1 - DNA 结合 37%、51% 和 65%。将 AFB1 与 350 μM 的 I3C、RXM 或 I33' 共同注射到虹鳟鱼胚胎中，1 年后 AFB1 诱导的肝癌发生率从阳性对照组的 43.4% 分别降至 36.0%、12.2%（P < 0.05）和 24.6%（P < 0.05）。由于孵化后胚胎存活率低，AFB1 加 CT 组未获得肿瘤数据。这些结果表明，酸性缩合产物而非母体化合物是虹鳟鱼中的抗癌物质，并且它们在胃中的形成可能是 I3C 抗癌作用的必要前提。
