Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats
Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats
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DOI：
10.1093/carcin/18.8.1535
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发表时间：
1997-08-01
期刊：
影响因子：
4.7
通讯作者：
Rowland, IR
中科院分区：
文献类型：
--
作者：
Hambly, RJ;Rumney, CJ;Rowland, IR
用人类肠道菌群定植的无菌大鼠喂食含有结直肠癌高风险（HR）或低风险（LR）因素的饮食，并评估结肠黏膜中可能的生物标志物；(i)增殖，（ii） 1,2-二甲基肼（DMH）诱导的异常隐窝灶和（iii） DMH诱导的DNA损伤。HR日粮脂肪含量高（45%的热量），钙和纤维含量低，反映了典型西方日粮的水平特征，LR日粮脂肪含量低（< 5%的热量），钙和纤维含量高，两种日粮的营养能量比相似，粘膜隐窝细胞增殖，经显微解剖评估。平均每隐窝有丝分裂数，LR组为2.65，I-IR组为1.62；P < 0.05),异常的地穴焦点(ACF)评估在粘膜DMH治疗12周后,人力资源部饮食有更小的ACF每关注1和2隐窝,但是更少的ACF 3、5和7每集中或多个隐窝,没有显著差异总ACF或隐窝的总数,饮食对DNA损伤的影响在结肠内被彗星试验评估体内,动物喂养12周的人力资源或LR的饮食治疗之前DMH或生理盐水,对于被致癌物处理过的动物，食用高致癌物的动物的结肠细胞DNA损伤明显更高，而食用低致癌物的动物，尽管细胞增殖增加，但DNA损伤和小ACF的诱导都减少了。低致癌物饮食中大ACF的增加可能是由于隐窝细胞增殖增加，可能增加了隐窝裂变率。
Germ-free rats colonised with a human intestinal flora were fed diets containing high risk (HR) or low risk (LR) factors for colorectal cancer, and putative biomarkers were evaluated in the colonic mucosa; (i) proliferation, (ii) 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci and (iii) DMH-induced DNA damage, The HR diet was high in fat (45% of calories) and low in calcium and fibre, reflecting levels characteristic of typical western diets, The LR diet was low in fat (< 5% of calories), and high in calcium and fibre, The nutrient/energy ratio of the two diets were similar, Mucosal crypt cell proliferation, assessed after microdissection, was higher on the LR diet (mean number of mitoses per crypt was 2.65 on the LR diet, and 1.62 on the I-IR diet; P < 0.05), Aberrant crypt foci (ACF) were assessed in the mucosa 12 weeks after DMH treatment, On the HR diet there were significantly more small ACF with 1 and 2 crypts per focus, but fewer ACF with 3, 5 and 7 or more crypts per focus, There was no significant difference in total ACF or the total number of crypts, The effect of diet on DNA damage in the colon was assessed in vivo by the comet assay, Animals were fed a HR or LR diet for 12 weeks before treatment with DMH or saline, For carcinogen-treated animals, DNA damage was significantly higher in colon cells from animals on the HR diet, On the LR diet both DNA damage and the induction of small ACF were reduced despite an increase in cell proliferation, The increase in large ACF on the LR diet may be attributable to elevated crypt cell proliferation possibly increasing crypt fission rates.