Objectif 1) To assess the role of genetically-determined variability of sulfotransferase (ST) expression in susceptibility to cancer induced by environmental agents.2) To investigate the incidence of polymorphic expression of phenol sulfotransferase (PST) in the following groups : a) individuals who have contracted bladder cancer as a result of documented and characterised exposure to aromatic amines; b) individuals who have documented exposure to aromatic amines but who failed to develop bladder cancer; c) individuals with cancer of the colon (where aromatic amines in the diet are suspected to play a significant role); and d) a group of healthy volunteers. High levels of expression of PST may result in increased susceptibility to carcinogenesis following exposure to these compounds, since they are bioactivated by STs.3) To study the molecular basis for the human phenol sulfotransferase polymorphism.4) To develop a simple diagnostic test, ideally based on the polymerase chain reaction, for the human phenol sulfotransferase polymorphism.Exposure to chemicals present in the environment, in the broadest sense, is one of the major causes of human cancer. The ability to predict those at genetic risk from chemical-induced cancers would have a major impact on the incidence of these diseases. Such an ambitious goal can only be achieved through a thorough understanding of the processes whereby exposure to environmental chemicals results in the molecular and cellular changes associated with carcinogenesis. This proposal focusses on an enzyme system - sulfotransferase (ST) - which is known to bioactivate certain environmental procarcinogens, resulting in the formation of highly reactive species which are capable of adducting to DNA. The isoenzyme of ST, as this is a multi-gene family, which is principally responsible for these bioactivation reactions, particularly with aromatic amines, is subject to polymorphic expression in the human population. We therefore propose to investigate this polymorphic variation in ST expression in individuals who have developed cancer as a result of exposure to environmental chemicals.We have chosen to study two groups of individuals, one very well defined group who have had documented exposure to aromatic amines, some of whom have developed cancer of the urinary bladder, and a second group of individuals who have cancer of the colon, where ingestion of aromatic amines from the diet (particularly cooked meats) is suggested to be involved in the pathogenesis of the disease. Our studies will type these individuals for the ST polymorphism and determine the relationship between the expression of the enzyme and susceptibility to cancer.Further to this, and to enable such studies to become more widely applicable, we aim to determine the molecular basis of this polymorphism, and to develop a simple method(s) to determine sulfator status of individuals using the polymorase chain reaction (PCR).The programme will lead to enhanced appreciation of the role of bioactivation of chemicals by this route and increased understanding of the molecular basis of susceptibility to chemical-induced cancer. Champ scientifique medical and health sciencesclinical medicineoncologybladder cancermedical and health scienceshealth sciencesnutritionnatural sciencesearth and related environmental sciencesenvironmental sciencespollutionnatural scienceschemical sciencesorganic chemistryaminesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994 Thème(s) 040204 - Risks to health and the environment from chemical substances Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur University of Dundee Contribution de l’UE Aucune donnée Adresse Ninewells Hospital and Medical School DD1 9SY Dundee Royaume-Uni Voir sur la carte Coût total Aucune donnée Participants (4) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Bayer AG Allemagne Contribution de l’UE Aucune donnée Adresse 51368 Leverkusen Voir sur la carte Coût total Aucune donnée Johannes-Gutenberg-Universität Mainz Allemagne Contribution de l’UE Aucune donnée Adresse Obere Zahlbacherstraße 67 55131 Mainz Voir sur la carte Coût total Aucune donnée Kreiskrankenhaus Gross-Gerau Allemagne Contribution de l’UE Aucune donnée Adresse Wilhelm-Seipp-Straße 64521 Goss-Gerau Voir sur la carte Coût total Aucune donnée University of Dundee Royaume-Uni Contribution de l’UE Aucune donnée Adresse Ninewells Hospital and Medical School DD1 9SY Dundee Voir sur la carte Coût total Aucune donnée
