Takahashi N, Dashwood R H, Bjeldanes L F, Williams D E, Bailey G S
Department of Food Science & Technology, Oregon State University, Corvallis 97331, USA.
Food Chem Toxicol. 1995 Oct;33(10):851-7. doi: 10.1016/0278-6915(95)00054-6.
Possible inhibitory mechanisms of indole-3-carbinol (I3C) against aflatoxin B1 (AFB1), a potent hepatocarcinogen, were examined in rainbow trout. In the Salmonella assay using a trout post-mitochondrial activation system, I3C itself was not an antimutagen against AFB1. The study also evaluated: the antimutagenic ability of I3C oligomers; an acid reaction mixture (RXM) of I3C, generated at low pH to simulate I3C products formed under acidic conditions of the stomach; 3,3-diindolylmethane (I33'), the major derivative of I3C found in trout liver; and 5,6,11,12,17,18- hexahydrocyclononal [1,2-b:4,5-b':7,8-b"]triindole , the cyclic trimer of I3C (CT), a derivative of I3C in liver and one of the major components of RXM. Concentrations of 3.5 microM and greater of I33', CT or RXM showed about 80% inhibition compared with the control. Higher concentrations (70 microM) of the various I3C oligomers also inhibited (to a maximum of 55%) mutagenesis of synthetic AFB1-8,9-epoxide added to the Salmonella assay, in the absence of activating enzymes. I33' inhibited total microsome catalysed AFB1-DNA binding in vitro in an apparently non-competitive manner (Kis = 27.6 +/- 9.4 microM, Kii = 37.5 +/- 32.2 microM). These results suggest that the anticarcinogenic effect of I3C against AFB1 in rainbow trout, and perhaps other species, is due in part to inhibition of AFB1 bioactivation enzymes and to scavenging of the activated AFB1-8,9-epoxide.
在虹鳟鱼中研究了吲哚 - 3 - 甲醇（I3C）对强效肝癌致癌物黄曲霉毒素B1（AFB1）的可能抑制机制。在使用虹鳟鱼线粒体后激活系统的沙门氏菌试验中，I3C本身对AFB1不是抗诱变剂。该研究还评估了：I3C低聚物的抗诱变能力；在低pH值下生成的I3C酸性反应混合物（RXM），用于模拟在胃酸性条件下形成的I3C产物；3,3 - 二吲哚甲烷（I33'），虹鳟鱼肝中发现的I3C主要衍生物；以及5,6,11,12,17,18 - 六氢环壬烷[1,2 - b:4,5 - b':7,8 - b"]三吲哚，I3C的环状三聚体（CT），是肝中I3C的衍生物和RXM的主要成分之一。与对照相比，I33'、CT或RXM浓度达到3.5 microM及更高时显示出约80%的抑制率。在没有激活酶的情况下，各种I3C低聚物的较高浓度（70 microM）也抑制了添加到沙门氏菌试验中的合成AFB1 - 8,9 - 环氧化物的诱变（最大抑制率为55%）。I33'以明显的非竞争性方式抑制体外总微粒体催化的AFB1 - DNA结合（Kis = 27.6 +/- 9.4 microM，Kii = 37.5 +/- 32.2 microM）。这些结果表明，I3C对虹鳟鱼以及可能对其他物种中AFB1的抗癌作用部分归因于对AFB1生物激活酶的抑制以及对活化的AFB1 - 8,9 - 环氧化物的清除。
