Graduate Program of General and Applied Biology, Biosciences Institute, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Department of Pathology, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil.
Br J Nutr. 2023 Feb 14;129(3):395-405. doi: 10.1017/S0007114522001350. Epub 2022 May 4.
Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. ( (AP) contains bioactive compounds with beneficial effects /. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1-G3) or vehicle (G4-G5) twice a week (weeks 3-4). During weeks 1-4, animals were fed a diet containing 1 % (G2) or 2 % (G3-G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, -H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2-G3) significantly decreased the DMH-induced increase in -H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, (Drug metabolism), , and genes (Notch pathway) and genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2-G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.
结直肠癌是全球第三大被诊断出的癌症，与饮食/生活方式因素有关。（（AP）含有具有有益作用的生物活性化合物。我们评估了 AP 喂养对 1,2-二甲基肼（DMH）诱导的结肠癌变的影响。雄性 Sprague Dawley 大鼠接受皮下注射 DMH（4×40mg/kg 体重）（G1-G3）或载体（G4-G5），每周两次（第 3-4 周）。在第 1-4 周期间，动物喂食含有 1%（G2）或 2%（G3-G4）AP 粉（w/w）的饮食。在此期间后，所有组均接受平衡饮食直至第 12 周。一些动物在最后一次 DMH 注射后（第 4 周）安乐死，用于组织学、免疫组织化学（Ki-67、-H2AX 和 caspase-3）和分子分析（91 个基因的实时 PCR），而其他动物在第 12 周安乐死用于分析前癌变异常隐窝病灶（ACF）。两种 AP 处理（G2-G3）在第 4 周时显著降低了 DMH 诱导的结肠隐窝中 -H2AX（DNA 损伤）和 caspase 3（DNA 损伤诱导的细胞死亡）的增加。此外，（药物代谢）、、和（Notch 途径）和（DNA 修复）基因在第 4 周时也被 2%AP 喂养（G3）下调。在第 12 周时，在两个 AP 处理组（G2-G3）中均观察到 ACF 发育的显著减少。结论表明，AP 喂养减少了 DMH 后急性结肠损伤，导致前癌变病变减少。我们的研究提供了关于 AP 饮食预防早期结肠癌发生的机制见解。
