Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats |
| |
Authors: | Hambly RJ; Rumney CJ; Cunninghame M; Fletcher JM; Rijken PJ; Rowland IR |
| |
Institution: | BIBRA International, Carshalton, Surrey, UK. |
| |
Abstract: | 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 HR 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.
|
| |
Keywords: | |
本文献已被 Oxford 等数据库收录! |
|