Cohen L A, Zhao Z, Zang E, Rivenson A
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, NY 10595, USA.
Carcinogenesis. 1996 Jan;17(1):45-52. doi: 10.1093/carcin/17.1.45.
The dose-related effects of the fiber-rich isolate, soft white wheat bran (SWWB), and the pure fiber, cellulose, on N-nitrosomethylurea (NMU)-induced mammary tumorigenesis was assessed in F344 female rats. SWWB (45% total dietary fiber, TDF) was added to the AIN-76A high-fat diet at 9, 12, 15 and 18%; cellulose (98% TDF) was added to the same diet at 4.5, 6, 7.5 and 9%, to give equivalent amounts of TDF. The experimental diets were fed 3 days post-NMU and continued for a period of 25 weeks, at which time the experiment was terminated and tumors enumerated. It was found that significant inhibition of mammary carcinoma occurred only at 9% SWWB, non-significant inhibition occurred at 12% SWWB, and no inhibition was seen at higher doses. Cellulose-fed animals exhibited consistently higher tumor yields regardless of dose. The difference in tumor yields between the 9% SWWB group and the remaining seven groups was attributable to an increased incidence in tumors characterized histologically as intraductal proliferation and ductal carcinoma in situ in the latter. Analysis of blood, urine and fecal estrogens was conducted to test whether dietary fiber exerted its tumor-inhibiting effect by altering the enterohepatic recycling of estrogens. Although SWWB, in general, lowered urinary estrogen excretion, increased fecal estrogen excretion and lowered blood estrogens, there was no consistent correlation between the amount of SWWB consumed, estrogen status and tumor yields. These results suggest that (i) wheat bran fiber at 9%, or minor constituents associated with it, contain anti-promoting properties that cellulose lacks; (ii) SWWB appears to exert its effects by suppressing the clonal expansion phase of mammary carcinogenesis; (iii) there is an upper limit (12-15% w/w) to the protective effects of SWWB; and (iv) the effects of SWWB on mammary tumorigenesis may not be attributed to alterations in the enterohepatic recycling of estrogens.
在F344雌性大鼠中评估了富含纤维的分离物软质白小麦麸（SWWB）和纯纤维纤维素对N-亚硝基甲基脲（NMU）诱导的乳腺肿瘤发生的剂量相关效应。将SWWB（总膳食纤维含量为45%，TDF）以9%、12%、15%和18%的比例添加到AIN-76A高脂饮食中；将纤维素（TDF含量为98%）以4.5%、6%、7.5%和9%的比例添加到相同饮食中，以使TDF含量相等。在给予NMU后3天开始喂食实验性饮食，并持续25周，此时实验终止并对肿瘤进行计数。结果发现，仅在SWWB含量为9%时对乳腺癌有显著抑制作用，在SWWB含量为12%时有非显著抑制作用，而在更高剂量时未观察到抑制作用。无论剂量如何，喂食纤维素的动物的肿瘤发生率始终较高。9%SWWB组与其余七组之间肿瘤发生率的差异归因于后者组织学上特征为导管内增生和原位导管癌的肿瘤发生率增加。对血液、尿液和粪便中的雌激素进行了分析，以测试膳食纤维是否通过改变雌激素的肠肝循环来发挥其肿瘤抑制作用。尽管总体而言，SWWB降低了尿液中雌激素的排泄，增加了粪便中雌激素的排泄并降低了血液中的雌激素，但所摄入的SWWB量、雌激素状态与肿瘤发生率之间没有一致的相关性。这些结果表明：（i）9%的麦麸纤维或与其相关的次要成分具有纤维素所缺乏的抗促进特性；（ii）SWWB似乎通过抑制乳腺肿瘤发生的克隆扩增阶段来发挥其作用；（iii）SWWB的保护作用存在上限（12 - 15% w/w）；（iv）SWWB对乳腺肿瘤发生的影响可能不归因于雌激素肠肝循环的改变。
