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Assessment of human exposure to reactive metabolites of dietary genotoxins - FS1715
The major heterocyclic amines (HAs) formed during the
cooking of food, PhIP and MeIQx are carcinogenic in animals.
This depends upon activation by CY
1A2, an enzyme that
varies markedly in its content and specificity between
species. Studies on the risk of HAs to man must therefore be
performed in humans. Methods will be devised to assess
human exposure to the active metabolities of these HAs.
These wil be based on sensitive chemical and immunological
techniques for measurement of adducts of the HAs with
protein and DNA, as well as specific sequences. The HAs will
serve as a paradigm for the development of better assays of
genotoxin exposure in man.
To devise novel, sensitive methods to enable the extent to
which humans are exposed to the reactive metabolities of
mutagenic heterocyclic amines present in cooked foods to be
assessed in vivo. Assaya for adducts with protein and DNA
will be devised for use as biomarkers for heterocyclic amine
in cooked food, can modulate heterocyclic amine activation
will also be addressed.
2) These studies should enable a valid risk assessment to
made of heterocyclic amines in cooked food. It should be
possible to use the information and the assays devised to
assess the relative risk of differentdiets, and to identify
anti-carcinogenic and co-carcinogenic factors in the diet.
The methods developed should be applicable to larger studies
of factors affecting exposure to the active metabolite. In
addition, they will enable similar atrategies to be
developed for other putative genotoxins in the diet. This
will enable dietary risks to be ranked and to identify the
importance of the diet as a whole in this.
Time-Scale and Cost
Contractor / Funded Organisations
Royal Postgraduate Medical Sch, Clin. Ph