Koch Tatiana C L, Briviba Karlis, Watzl Bernhard, Bub Achim, Barth Stephan W
Department of Nutritional Physiology and Biochemistry, Max Rubner-Institute, Haid-und-Neu-Strasse 9, 76131 Karlsruhe, Germany.
Eur J Nutr. 2008 Apr;47(3):161-70. doi: 10.1007/s00394-008-0711-1. Epub 2008 May 15.
Obesity and energy restriction modulate the development of precancerous aberrant crypt foci (ACF) in animal models of colon cancer.
Investigation of the major obesity-associated determinants for ACF-development and underlying mechanisms leading to ACF-modulation, such as changes in DNA damage or colonocytes hyperproliferation.
Lean and obese Zucker rats fed ad libitum (a.l.) or obese pair fed (p.f.) were induced with 1,2-dimethylhydrazine (DMH) for colon cancer. Multiple regression analyses were performed to identify major metabolic factors correlated with ACF number and size (aberrant crypts/ACF). DNA damage is analyzed by the comet-assay, epithelial proliferation by immunohistochemistry.
Aberrant crypt foci number was significantly elevated in Zucker obese a.l. (205.7+/-65.4 vs. lean 9.5+/-6.3, P<0.05) and is reduced by pair feeding in Zucker obese rats (81.4+/-28.5 vs. obese a.l., P<0.05). Compared to lean the ACF size was higher in Zucker obese a.l. (2.1+/-0.3 vs. lean 1.3+/-0.2., P<0.05) but is not reduced by pair feeding (1.7+/-0.2; P>0.05). While ACF number and size were modulated by genotype and/or pair feeding the DMH-induced DNA damage and hyperproliferation in colonocytes did not differ significantly between groups. Regression analysis showed that plasma parameters associated with lipid-metabolism (triglycerides, cholesterol, malondialdehyde) significantly correlated with the ACF number and size while parameters linked to carbohydrate-metabolism (glucose, insulin) were weaker determinants.
Obesity or pair feeding-associated modulation of ACF correlate with parameters related to lipid-metabolism but is not accompanied by changes in DNA damage and proliferation.
在结肠癌动物模型中，肥胖和能量限制会调节癌前异常隐窝灶（ACF）的形成。
研究与ACF形成相关的主要肥胖相关决定因素以及导致ACF调节的潜在机制，如DNA损伤或结肠细胞过度增殖的变化。
对自由采食（a.l.）的瘦型和肥胖型Zucker大鼠或肥胖型配对喂养（p.f.）的大鼠用1,2 - 二甲基肼（DMH）诱导结肠癌。进行多元回归分析以确定与ACF数量和大小（异常隐窝/ACF）相关的主要代谢因素。通过彗星试验分析DNA损伤，通过免疫组织化学分析上皮细胞增殖。
Zucker肥胖自由采食组的异常隐窝灶数量显著增加（205.7±65.4对瘦型9.5±6.3，P<0.05），而Zucker肥胖大鼠通过配对喂养数量减少（81.4±28.5对肥胖自由采食组，P<0.05）。与瘦型相比，Zucker肥胖自由采食组的ACF大小更高（2.1±0.3对瘦型1.3±0.2，P<0.05），但配对喂养后未降低（1.7±0.2；P>0.05）。虽然ACF数量和大小受基因型和/或配对喂养调节，但各组间DMH诱导的结肠细胞DNA损伤和过度增殖无显著差异。回归分析表明，与脂质代谢相关的血浆参数（甘油三酯、胆固醇、丙二醛）与ACF数量和大小显著相关，而与碳水化合物代谢相关的参数（葡萄糖、胰岛素）是较弱的决定因素。
肥胖或配对喂养相关的ACF调节与脂质代谢相关参数有关，但不伴有DNA损伤和增殖的变化。
