el-Sohemy A, Kendall C W, Rao A V, Archer M C, Bruce W R
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ont., Canada.
Nutr Cancer. 1996;25(2):111-7. doi: 10.1080/01635589609514433.
We evaluated the effect of dietary cholesterol and oxidized cholesterol on the promotion of aberrant crypt foci (ACF), which are putative precancerous lesions in the colon. Sixty female C57BL/6J mice were given four weekly injections (ip) of azoxymethane (AOM) then fed either a control AIN-76 diet or the control diet supplemented with 0.3% cholesterol or 0.3% oxidized cholesterol for 100 days. The oxidized cholesterol was prepared by heating cholesterol at 110 degrees C for 48 hours. Gas chromatographic analysis of the oxidized cholesterol showed that 96% of the cholesterol was unchanged and less than 2% of the cholesterol was oxidized. The remaining 2% impurities were unidentified and present in both the cholesterol and heated cholesterol. The number of ACF in the group fed cholesterol was significantly lower than the control group (7.9 +/- 1.0 vs. 12.5 +/- 1.2, p < 0.01). The number of ACF in the group fed oxidized cholesterol (10.1 +/- 1.1) was not different from the control or cholesterol groups. The size of the ACF (no. of crypts per focus) did not differ between the three dietary groups. Serum low-density lipoprotein (LDL) cholesterol was greater in the cholesterol-fed group than the control group (40.5 +/- 4.6 vs. 24.3 +/- 3.6 mg/dl, p < 0.05). LDL cholesterol from the animals fed oxidized cholesterol (37.7 +/- 4.7 mg/dl) was not different from the control or cholesterol-fed animals. Total and high-density lipoprotein (HDL) cholesterol did not differ between the groups. The results show that dietary cholesterol significantly inhibits the promotion of ACF in the colon. The elevated LDL cholesterol may inhibit de novo cholesterol synthesis in the preneoplastic colonic epithelial cells, thereby inhibiting DNA synthesis and cell proliferation.
我们评估了膳食胆固醇和氧化胆固醇对结肠中假定的癌前病变——异常隐窝灶（ACF）形成的促进作用。60只雌性C57BL/6J小鼠每周腹腔注射一次偶氮甲烷（AOM），共注射四周，然后分别喂食对照AIN - 76饮食或添加0.3%胆固醇或0.3%氧化胆固醇的对照饮食，持续100天。氧化胆固醇是通过将胆固醇在110℃加热48小时制备的。对氧化胆固醇的气相色谱分析表明，96%的胆固醇未发生变化，不到2%的胆固醇被氧化。其余2%的杂质未鉴定出来，且在胆固醇和加热后的胆固醇中均有存在。喂食胆固醇组的ACF数量显著低于对照组（7.9±1.0对12.5±1.2，p<0.01）。喂食氧化胆固醇组的ACF数量（10.1±1.1）与对照组或胆固醇组无差异。三个饮食组之间ACF的大小（每个病灶的隐窝数量）没有差异。喂食胆固醇组的血清低密度脂蛋白（LDL）胆固醇高于对照组（40.5±4.6对24.3±3.6mg/dl，p<0.05）。喂食氧化胆固醇的动物的LDL胆固醇（37.7±4.7mg/dl）与对照组或喂食胆固醇的动物无差异。各组之间总胆固醇和高密度脂蛋白（HDL）胆固醇没有差异。结果表明，膳食胆固醇显著抑制结肠中ACF的形成。升高的LDL胆固醇可能抑制癌前结肠上皮细胞中胆固醇的从头合成，从而抑制DNA合成和细胞增殖。
