The mechanistic basis for providing a realistic cancer risk assesment for exposure to inorganic arsenic within the European Comunity - ASRISK

Exposure to inorganic arsenis from different sources is a major public health concern in many regions. In accordance with existing EU Guidelines for cancer risk assessment, and that is based on mechanism of action, the general aim of this project is to define "virtually safe " levels for arsenic based on elucidation of the basic process underlying the induction of genotoxic effects and cancer, taking into consideration differences in ethnical and individual susceptibility. While considering other mechanisms, like inhibition of p53 tumor suppressor gene function and somatic recombination and synergistic effects, one major task of this project is to demonstrate if arsenic inhibits DNA-repair in humans, a type of mechanism that implies a dose threshold for carcinogenic action. The dose-response relationship for in vivo induction of chromosomal aberrations will also be defined. A second major task is to explore the relation between detoxification (methylation) patterns, genetic polymorphism and susceptibility to the chronic toxic action of arsenic.