Document Detail

Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats.
MedLine Citation:
PMID:  9276627     Owner:  NLM     Status:  MEDLINE    
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.
R J Hambly; C J Rumney; M Cunninghame; J M Fletcher; P J Rijken; I R Rowland
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  18     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-10-14     Completed Date:  1997-10-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1535-9     Citation Subset:  IM    
BIBRA International, Carshalton, Surrey, UK.
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MeSH Terms
Biological Markers / analysis*
Body Weight / drug effects
Colon / drug effects,  pathology*
Colonic Diseases / chemically induced,  genetics,  pathology*
Colonic Neoplasms / chemically induced,  genetics,  pathology*
DNA / drug effects
Diet / adverse effects*
Disease Models, Animal
Food, Formulated
Germ-Free Life
Intestinal Mucosa / drug effects,  pathology*
Mitotic Index / drug effects
Precancerous Conditions / chemically induced,  pathology*
Rats, Inbred F344
Risk Factors
Reg. No./Substance:
0/Biological Markers; 0/Dimethylhydrazines; 540-73-8/1,2-Dimethylhydrazine; 9007-49-2/DNA

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