Kim Y I, Salomon R N, Graeme-Cook F, Choi S W, Smith D E, Dallal G E, Mason J B
Vitamin Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
Gut. 1996 Nov;39(5):732-40. doi: 10.1136/gut.39.5.732.
Diminished folate status is associated with enhanced colorectal carcinogenesis. This study investigated the potential chemopreventive role of dietary folate in the dimethylhydrazine colorectal cancer model.
Sprague-Dawley rats were fed diets containing either 0, 2 (daily dietary requirement), 8 or 40 mg folate/kg diet for 20 weeks. After five weeks of diet, rats were injected with dimethyl-hydrazine (44 mg/kg) weekly for 15 weeks. Fifteen weeks after the first injection of dimethylhydrazine, all rats were killed. Folate status was determined, and the entire colorectum from each rat was analysed for macroscopic and microscopic neoplasms.
Plasma and colonic folate concentrations correlated directly with dietary folate levels (p < 0.005). The incidence of microscopic neoplasms was similar among the four groups. However, the incidence and the average number of macroscopic tumours per rat decreased progressively with increasing dietary folate levels up to 8 mg/kg diet (p < 0.05). In the strongly procarcinogenic milieu used in this study, folate supplementation at 20 times the basal requirement was associated with rates of macroscopic tumour development that were intermediate, and not statistically distinct, from rates observed at either 0 or 8 mg/kg diet.
These data indicate that in this rat model, (a) increasing dietary folate up to four times the basal requirement leads to a progressive reduction in the evolution of macroscopic neoplasms from microscopic foci; and (b) folate supplementation beyond four times the requirement does not convey further benefit.
叶酸水平降低与结直肠癌发生风险增加有关。本研究在二甲基肼诱导的结直肠癌模型中探讨了膳食叶酸的潜在化学预防作用。
将斯普拉格-道利大鼠分为四组，分别给予含0、2（每日膳食需求量）、8或40mg叶酸/kg饲料的饮食，持续20周。饮食5周后，大鼠每周注射一次二甲基肼（44mg/kg），共15周。首次注射二甲基肼15周后，处死所有大鼠。测定叶酸水平，并对每只大鼠的整个结肠直肠进行大体和显微镜下肿瘤分析。
血浆和结肠叶酸浓度与膳食叶酸水平直接相关（p<0.005）。四组之间显微镜下肿瘤的发生率相似。然而，随着膳食叶酸水平增加至8mg/kg饲料，每只大鼠大体肿瘤的发生率和平均数量逐渐降低（p<0.05）。在本研究使用的强致癌环境中，补充20倍于基础需求量的叶酸后，大体肿瘤的发生速率处于中间水平，与0或8mg/kg饲料组相比无统计学差异。
这些数据表明，在该大鼠模型中，（a）将膳食叶酸增加至基础需求量的四倍可使大体肿瘤从微小病灶的演变逐渐减少；（b）补充超过四倍需求量的叶酸不会带来进一步益处。
