He Y H, Smale M H, Schut H A
Department of Pathology, Medical College of Ohio, Toledo 43614-5806, USA.
J Cell Biochem Suppl. 1997;27:42-51. doi: 10.1002/(sici)1097-4644(1997)27+<42::aid-jcb9>3.0.co;2-1.
Indole-3-carbinol (I3C), a naturally occurring inhibitor of experimental carcinogenesis, was evaluated for its possible inhibitor effect on DNA-adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary mutagen, in female F344 rats. PhIP is a mammary carcinogen in female F344 rats and a colon carcinogen in male F344 rats. Four-week-old animals (4/group) were maintained on powdered AIN-76A diet with or without 13C (0.02% or 0.1%, w/w) for 58 days. PhIP (0.04%, w/w) was added to the diet from days 15 through 42. Animals were killed on days 43 and 58. DNA isolated from mammary epithelial cells (MECs), colon, liver, and white blood cells (WBCs) was analyzed for PhIP-DNA adducts by 32P-postlabeling assays. On day 43, adduct levels of the group receiving 0.1% dietary I3C decreased in MECs (91.9%), colon (67.2%), liver (69.2%), and WBCs (82.3%). On day 58, DNA adduct formation was inhibited in the colon (81.3-82.2%) at both dietary I3C concentrations, and in liver (46.8%) only in the animals fed 0.1% I3C. When incorporated in the diet after exposure to dietary PhIP (0.04% for 2 weeks), 13C (0.1%) had no effect on the rate of removal of PhIP-DNA adducts over the next 28 days. It is concluded that dietary I3C inhibits PhIP-DNA adduct formation in the female F344 rat but does not affect adduct removal. I3C may be a promising chemopreventive agent in PhIP-induced carcinogenesis in rats.
吲哚 - 3 - 甲醇（I3C）是一种天然存在的实验性致癌抑制剂，本研究评估了其对2 - 氨基 - 1 - 甲基 - 6 - 苯基咪唑[4,5 - b]吡啶（PhIP，一种膳食诱变剂）在雌性F344大鼠体内DNA加合物形成的潜在抑制作用。PhIP是雌性F344大鼠的乳腺致癌物和雄性F344大鼠的结肠致癌物。将四周龄动物（每组4只）饲养在含或不含I3C（0.02%或0.1%，w/w）的AIN - 76A粉状饲料中58天。从第15天到第42天，在饲料中添加PhIP（0.04%，w/w）。在第43天和第58天处死动物。通过³²P后标记分析法分析从乳腺上皮细胞（MECs）、结肠、肝脏和白细胞（WBCs）中分离的DNA的PhIP - DNA加合物。在第43天，摄入0.1%膳食I3C组的MECs（91.9%）、结肠（67.2%）、肝脏（69.2%）和WBCs（82.3%）中的加合物水平下降。在第58天，两种膳食I3C浓度下结肠中的DNA加合物形成均受到抑制（81.3 - 82.2%），而仅在饲喂0.1% I3C的动物肝脏中加合物形成受到抑制（46.8%）。当在暴露于膳食PhIP（0.04%，持续2周）后掺入饲料中时，I3C（0.1%）在接下来的28天内对PhIP - DNA加合物的去除速率没有影响。得出的结论是，膳食I3C可抑制雌性F344大鼠体内PhIP - DNA加合物的形成，但不影响加合物的去除。I3C可能是大鼠中PhIP诱导致癌作用的一种有前景的化学预防剂。
