The Gerhard Zbinden memorial lecture: application of biochemical and genetic approaches to understanding pathways of chemical toxicity.
All cells have evolved a complex number of pathways, which allow them to survive in a chemically hostile environment. In multicellular organisms, these pathways are catalysed by a number of key enzymes, which inhibit the absorption of toxins or facilitate their elimination so that they do not accumulate to toxic levels within the cell. These cytoprotective pathways are also critical determinants of the effectiveness of drug therapy and are thought to have evolved from a limited number of biochemical pathways, such as those which allow cells to utilise molecular oxygen in respiration without suffering deleterious effects. The study of both simple and multicellular organisms has shown that many stress response pathways previously considered as distinct adaptive mechanisms in mammalian systems are interrelated coordinated responses to toxic challenge. Understanding the functions and mechanisms of regulation of the genes involved in these pathways has many applications in medical science-in evaluating the role of environmental factors in the pathogenesis of human disease, in chemoprevention, in drug development and in the application of drug therapy. The use of genetic approaches, coupled with new chip-based profiling technologies, will play a key role in the development of studies in this research area.
Wolf
C Roland
CR
ICRF Molecular Pharmacology Unit/Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Scotland DD1 9SY, UK. rooney@icrf.icnet.uk
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000378:metabolism / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D004785:Environmental Pollutants; D016159:Tumor Suppressor Protein p53; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase