Nixon J E, Hendricks J D, Pawlowski N E, Pereira C B, Sinnhuber R O, Bailey G S
Carcinogenesis. 1984 May;5(5):615-9. doi: 10.1093/carcin/5.5.615.
Several compounds such as flavonoids, selenium, antioxidants and retinoids reportedly reduce the induction of cancer in experimental animals, and some have been suggested to function by affecting the mixed-function oxidase (MFO) system. The following compounds: 50 and 500 p.p.m. beta-naphthoflavone (BNF), 1000 p.p.m. flavone, 1000 p.p.m. of a tangeretin - nobilitin mixture, 1000 p.p.m. beta- ionone , 1000 p.p.m. indole-3-carbinol ( I3C ) and 2000 p.p.m. quercetin were examined for protection against aflatoxin B1 (AFB1) hepatocarcinogenesis, induction of the MFO system and metabolism of AFB1 in rainbow trout. These compounds were fed to fingerling rainbow trout for 8 weeks. At that time the activity of several MFO enzymes and cytochrome P450 content were measured and the trout were exposed for 2 weeks to 20 p.p.b. AFB1 in the same diets. After feeding the test diets without AFB1 for another 6 weeks and basal diet for another 52 weeks, the tumor incidence was determined. The effect of BNF and I3C on in vivo binding of AFB1 to DNA was also measured in separate groups of trout. BNF induced the trout MFO system in a dose-dependent manner, tangeretin - nobilitin was less effective and I3C did not induce. BNF showed significant alterations in the metabolism of AFB1 to aflatoxicol and aflatoxin M1 using cell fractions from pretreated fish. None of the other compounds, including I3C showed such an effect. Despite the apparent lack of in vitro effect of I3C , both BNF and I3C reduced AFB1 - DNA binding in vivo. I3C and BNF provided marked protection against AFB1-induced hepatocarcinogenesis, while the other compounds were less effective. The 58 weeks tumor incidences were 4% for 1000 p.p.m. I3C , 6% for 500 p.p.m. BNF and 18% for 50 p.p.m. BNF, compared to 38% for the AFB1-positive control. These data demonstrate that gross induction of the MFO system was not necessarily required for alterations in DNA adduct formation in vivo or protection against AFB1 carcinogenesis. Both BNF and I3C provided marked protection but only BNF induced the MFO system.
据报道，黄酮类化合物、硒、抗氧化剂和类视黄醇等几种化合物可降低实验动物体内癌症的诱发率，并且有人认为其中一些化合物是通过影响混合功能氧化酶（MFO）系统发挥作用的。对以下化合物进行了检测：50和500 ppm的β-萘黄酮（BNF）、1000 ppm的黄酮、1000 ppm的柑橘黄酮-诺比灵混合物、1000 ppm的β-紫罗兰酮、1000 ppm的吲哚-3-甲醇（I3C）以及2000 ppm的槲皮素，以研究它们对虹鳟鱼黄曲霉毒素B1（AFB1）致癌作用、MFO系统诱导以及AFB1代谢的防护作用。将这些化合物投喂给虹鳟鱼苗8周。之后测定几种MFO酶的活性和细胞色素P450含量，并让虹鳟鱼在相同饲料中接触20 ppb的AFB1，持续2周。在投喂不含AFB1的试验饲料6周以及基础饲料52周后，测定肿瘤发生率。还在另一组虹鳟鱼中检测了BNF和I3C对AFB1在体内与DNA结合的影响。BNF以剂量依赖方式诱导虹鳟鱼的MFO系统，柑橘黄酮-诺比灵的效果较差，而I3C未产生诱导作用。使用预处理鱼的细胞组分，BNF使AFB1代谢为黄曲霉毒素醇和黄曲霉毒素M1的过程发生了显著变化。包括I3C在内的其他化合物均未显示出这种效果。尽管I3C在体外似乎没有作用，但BNF和I3C在体内均降低了AFB1与DNA的结合。I3C和BNF对AFB1诱导的肝癌发生提供了显著的防护作用，而其他化合物的效果较差。1000 ppm的I3C、500 ppm的BNF和50 ppm的BNF在58周时的肿瘤发生率分别为4%、6%和18%，而AFB1阳性对照组为38%。这些数据表明，体内DNA加合物形成的改变或对AFB1致癌作用的防护不一定需要MFO系统的全面诱导。BNF和I3C均提供了显著的防护作用，但只有BNF诱导了MFO系统。
