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This research project seeks to develop a new model to address interactions between genotoxic and non-genotoxic food components of diets.
<p>Diet may be implicated in the 20-fold international variance of colorectal cancer (CRC). Consumption of some processed meat exposes humans to N-nitroso compounds (NOCs), undegraded carrageenan and may confer increased risk of CRC.
<p>Understanding of interactive effects of dietary chemicals upon initiation and progression of colonic tumourigenesis are limited. Dietary risk assessment is particularly hampered by the lack of a mechanistically based predictive model.
<p>This project tests the hypothesis that markers of colonic crypt stem cell mutation may provide the scientific basis for a predictive model.
<p>This project seeks to address interactive effects of genotoxic and non-genotoxic food components and to develop biomarkers of food toxicity that may aid risk assessment.
Test chemicals were chosen to model patterns similar to real life human exposures and to represent other environmental agents that share similar toxic mechanisms of effect.
<p>N-methyl-N-nitrosurea (MNU) is a mutagenic NOC while undegraded lambda carrageenan (ëCgN) is a non-genotoxic agent with pro-oxidant properties. Within the model, the MNU dose was held constant while exposure conditions of ëCgN were varied.
<p>Endpoints included DNA damage, metallothionein (MT) crypt restricted immunopositivity indices (MTCRII), which are colonic crypt stem cell mutation markers, and aberrant crypt foci (ACF) which represent the earliest morphological precursors of colorectal cancer.
<p>MTCRII are intermediate markers, developing within 4-6 weeks of chemical treatment. The predictive power of MTCRII was then assessed against later development of ACF, at 20 weeks after treatment.
<p>Find more about this project and other FSA food safety-related projects at the <a href="http://www.food.gov.uk/science/research/" target="_blank">Food Standards Agency Research webpage</a>.