BioMatNet Item: FAIR-CT95-0894 - Phenolic phytoprotectants - role in preventing initiation, promotion and progression of cancer

FAIR-CT95-0894
Phenolic phytoprotectants - role in preventing initiation, promotion and progression of cancer

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Biotechnology : FAIR Area 3 - Generic Science and Advanced Technologies for Nutritious Foods : Pharmaceuticals/Cosmetics

	Type of Project	Shared Cost
	Contract No	FAIR-CT95-0894
	Total Cost	1,790,259 ECU
	EC Contribution	1,041,941 ECU
	Start Date	01/01/1996
	Duration	36 Months

Phenolic phytoprotectants - role in preventing initiation, promotion and progression of cancer

Objectives

The objectives of the project are:

to extract, identify and quantify phenolic phytoprotectants (PPPs) in plants and processed foods
to evaluate anti-cancer effects of PPPs
to assess the bioavailability of PPPs
to evaluate the role of intestinal microflora and membrane function in these processes

Technical Approach

Limited epidemiological and experimental data suggest that PPPs may help to prevent cancer. The overall objective of this project is to identify and quantify phenolic phytoprotectants in plants and foods, assess their bioavailability and the role of intestinal microflora in their bioavailability and metabolism as well as evaluate anticancer effects and their mechanisms.

The group of analytical and synthetic tasks include:

development of novel methods for the analysis of PPPs in food samples and biological fluids.
analysis by GC-MS of major PPPs (lignans isoflavonoids, flavonoids and alkylresorcinols) in different varieties of plants and plant food, and in grain grown in different agronomic conditions and study the effects of food processing on PPPs.
quantify PPP metabolites in human and animal samples, and in samples form in vitro studies.
provide standards including radiolabelled and stable isotope derivatives for use in assays by other participants.

The group of tasks involving studies on metabolism, bioavailability, mechanism of action and carcinogenicity studies include:

assess the role of gut flora in the metabolism and bioavailability of PPPs
investigations on the individual variation in bioavailability and metabolism in human subjects (pharmacokinetic studies)
investigate the activity of PPPs and their metabolites in a number of novel biological assays for antigenotoxicity and anticarcinogenicity

The group of tasks involving in vivo studies in animals and effects on biomarkers in human volunteer studies include:

studies on the absorption, bioavailability and tissue distribution (only in rats) of radioisotope-labelled PPPs (alkylresorcinols) in animal models and human volunteers
provide evidence for anti-carcinogenicity of selected PPPs in colon, breast and prostate cancer using genetically engineered mice and other in vivo tumour models

The project will provide EU industries with important information for the development of new generations of foods with health promoting effects.

Results to Date

A number of new methods for the immunological, GC-MS and HPLC assay of PPPs in biological fluids, tissues and foods were developed. These methods were extensively used in metabolic (human and animal), pharmacokinetic and bioavailability studies as well as in studies on the effect of intestinal microflora on metabolism of PPPs. A large number of food (processed and unprocessed) analyses on 7 PPPs were carried out. Large between-individual variations in PPP metabolism were found and a significant effect of diet on this metabolism was observed. The antigenotoxic potential of isoflavonoids and lignans has been studied by assessing their ability to protect cells against induction of oxidation of pyrimidine or purine bases. Apc-deficient Min mice were bred and high-risk and low-risk diets were produced. Soy and rye bran (contains lignans) did not protect the mice from obtaining small intestinal tumours during a high-risk diet, and with regard to colon tumours negative results were obtained. Soy food, containing isoflavones, did not protect Apc^Min mice against intestinal neoplasia but rye bran inhibited the development the development of colon cancer in a rat model. Both soy and rye bran inhibited the development of prostate cancer implanted in rats or nude mice and caused an increased apoptosis but did not change proliferation rate.

Contacts

Coordinator

Herman ADLERCREUTZ / University of Helsinki, Folkhalsan Research Centre Division of Clinical Chemistry / FINLAND

EC Scientific Officer

Laurent BOCHEREAU / European Commission Biotechnology, Agriculture and Food Research / BELGIUM

Participant