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Title: The effect of diet on endogenous N-nitrosation and DNA damage
Author: Hughes, R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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Endogenous N-nitrosocompound (NOC) formation is one of the most potent-sources of human exposure to these potential carcinogens. The modulatory effects of diet on markers of colonic metabolism including faecal apparent total NOC (ATNC) excretion, and markers of DNA damage were investigated in this Thesis. Three human feeding trails with healthy male volunteers wee conducted under controlled metabolic conditions. Results showed that faecal ATNC excretion during high red (420 g/day) and white meat diets (600 g/day) was significantly greater than during a low meat diet (60 g/day) (p < 0.0001; p=0.04 respectively). In terms of red meat, this increase was dose dependent (p<0.0001 for dietary effects during two-way ANOVA). Faecal nitrite and ammonia excretion were also positively related to increased dietary meat. Meat is a source of iron which is required as a co-factor in nitrate reductase and endogenous NOC formation but no effect of an iron supplement with a low and high white meat diet on faecal ATNC was determined in a group of four volunteers. Supplementation of the high meat diet with vegetables and tea did not inhibit the increased faecal ATNC excretion even though these have been shown elsewhere to inhibit N-nitrosation in vitro and in animals. Faecal ATNC concentration was however suppressed when the high meat diet was supplemented with 100 g/day soya (p = 0.024). Soya is a source of the isoflavone genistein which inhibits the enzyme responsible for nitric oxide production (i.e. inducible NO synthase). NO produced by this enzyme is involved in NOC formation. Another iNOS inhibitor, aspirin, however did not show the same suppressive effect. 93% of the faecal water samples extracted during the meat, vegetable and tea study were genotoxic as determined by the COMET assay and no effect of diet was apparent.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available