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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
From: 1994

To: 1998

Cost: £339,498
Contractor / Funded Organisations
Royal Postgraduate Medical Sch, Clin. Ph