CONGENITAL DISORDERS SHARING OXIDATIVE STRESS AND CANCER PRONENESS ASPHENOTYPIC HALLMARKS - PROSPECTS FOR JOINT RESEARCH IN PHARMACOLOGY

In spite of very distinct genotypic assets, a number of congenital con ditions include oxidative stress as a phenotypic hallmark. These disor ders include Fanconi's anaemia, ataxia telangiectasia, xeroderma pigme ntosum and Bloom's syndrome, as well as two frequent congenital condit ions: Down's syndrome and cystic fibrosis. Cancer proneness is a clini cal feature shared by these disorders, while other manifestations incl ude early ageing, neurological symptoms or congenital malformations. T he onset of oxidative stress has been related to excess formation, or defective detoxification, of reactive oxygen species (ROS). This can a rise from either the abnormal expression or inducibility of ROS-detoxi fying enzymes, or by defective absorption of nutrient antioxidants. Re sulting oxidative injury has been characterized through: (i) DNA, prot ein or lipid oxidative damage; (ii) excess ROS formation (in vitro and ex vivo); (iii) sensitivity to oxygen- related toxicity; (iv) improve ment of cellular defects by either hypoxia or antioxidants; and (v) ci rcumstantial evidence for in vivo oxidative stress (as e.g. clastogeni c factors). Investigations conducted so far have been confined to indi vidual disorders. Comparative studies of selected indicators for oxida tive stress could provide further insights into the pathogenesis of ea ch individual condition. Such a unified approach may have wide-ranging consequences for studies of ageing and cancer.