Sesink A L, Termont D S, Kleibeuker J H, Van der Meer R
Nutrition and Health Programme, Wageningen Centre for Food Sciences, NIZO Food Research, PO Box 20, 6710 BA Ede, The Netherlands.
Carcinogenesis. 2001 Oct;22(10):1653-9. doi: 10.1093/carcin/22.10.1653.
High intake of red meat is associated with increased colon cancer risk. We have shown earlier that this may be due to the high haem content of red meat, because dietary haem increased cytolytic activity of faecal water and colonic epithelial proliferation. Dietary calcium inhibits diet-induced epithelial hyperproliferation. Furthermore, it has been shown that supplemental calcium inhibited the recurrence of colorectal adenomas. Therefore, we studied whether dietary calcium phosphate can exert its protective effects by inhibiting the deleterious effects of haem. In vitro, calcium phosphate precipitated haem and inhibited the haem-induced cytotoxicity. Subsequently, rats were fed diets, differing in haem (0 or 1.3 micromol/g) and calcium phosphate content only (20 or 180 micromol/g). Faeces were collected for biochemical analyses. Cytolytic activity of faecal water was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. In rats fed low calcium diets, dietary haem increased cytolytic activity of faecal water (98 +/- 1 versus 1 +/- 1%, P < 0.001) and the concentration of cations in faeces (964 +/- 31 versus 254 +/- 20 micromol/g), when compared with controls. This indicates that dietary haem increased colonic mucosal exposure to luminal irritants. Colonic epithelial proliferation was increased compared with controls (70 +/- 4 versus 48 +/- 8 d.p.m./microg DNA, P < 0.001). This was accompanied by metabolism of the ingested haem and solubilization of haem compounds in the faecal water. A high calcium diet largely prevented this metabolism and solubilization. It also inhibited the haem-induced cytolytic activity of faecal water and increase in faecal cation concentration. In accordance, the haem-induced colonic epithelial hyperproliferation was prevented. We therefore suggest that dietary calcium phosphate acts as a chemopreventive agent in colon carcinogenesis by inhibiting the cytolytic and hyperproliferative effects of dietary haem.
大量摄入红肉与结肠癌风险增加有关。我们之前已经表明，这可能是由于红肉中血红素含量高，因为膳食血红素会增加粪便水的细胞溶解活性和结肠上皮细胞增殖。膳食钙可抑制饮食诱导的上皮细胞过度增殖。此外，研究表明补充钙可抑制大肠腺瘤的复发。因此，我们研究了磷酸钙是否能通过抑制血红素的有害作用发挥其保护作用。在体外，磷酸钙沉淀血红素并抑制血红素诱导的细胞毒性。随后，给大鼠喂食仅在血红素（0或1.3微摩尔/克）和磷酸钙含量（20或180微摩尔/克）上不同的饮食。收集粪便进行生化分析。通过粪便水对红细胞的裂解程度来测定粪便水的细胞溶解活性。使用[³H]胸腺嘧啶核苷掺入法在体内测量结肠上皮细胞增殖。与对照组相比，喂食低钙饮食的大鼠，膳食血红素增加了粪便水的细胞溶解活性（98±1对1±1%，P<0.001）和粪便中阳离子浓度（964±31对254±20微摩尔/克）。这表明膳食血红素增加了结肠黏膜对腔内刺激物的暴露。与对照组相比，结肠上皮细胞增殖增加（70±4对48±8每分钟衰变数/微克DNA，P<0.001）。这伴随着摄入的血红素的代谢以及粪便水中血红素化合物的溶解。高钙饮食在很大程度上阻止了这种代谢和溶解。它还抑制了血红素诱导的粪便水细胞溶解活性和粪便阳离子浓度的增加。相应地，血红素诱导的结肠上皮细胞过度增殖也得到了预防。因此，我们认为膳食磷酸钙通过抑制膳食血红素的细胞溶解和过度增殖作用，在结肠癌发生过程中起到化学预防剂的作用。
