New aspects on mechanisms of chemical carcinogenesis: emphasis on species and gender/sex differences and developmental/aging determinants

Abstract

The workshop was organized on behalf of the European Network of Excellence (NoE) Environmental Cancer, Nutrition and Individual Susceptibility (ECNIS). ECNIS focuses on the utility of biomarkers relevant to assess environmental cancer risk. The most important components of the ECNIS science integration activities are scientiWc cooperations, intensive workshops focused on Environmental Cancer, Nutrition and Individual Susceptibility, various joint training and mobility programs including scientiWc meetings, exchange of researchers and shared laboratory facilities as well as joint training programs. An overall objective of ECNIS is to disseminate acquired knowledge to the scientiWc community as is intended with this Meeting Report. For further information on ECNIS see also http:// www.ecnis.org. A work package 10 “Mechanistic research to support cancer hazard and risk assessment” coordinated by Franz Oesch (University of Mainz, Germany) investigates the inXuence of various selected and still poorly understood determinants on mechanisms of carcinogenesis. Past eVorts gathered and revisited information on dose response relations in chemical carcinogenesis and the action of mixtures of carcinogens. In a recent workshop held in Debowa Gora, Poland on 24 April organized by Carsten Weiss (Research Centre Karlsruhe, Germany) and Franz Oesch together with Cornelia Dietrich and Barbara Oesch (University of Mainz, Germany) eVects of species and gender/sex diVerences as well as developmental and aging determinants in environmental cancer were presented and discussed. The multistep process of chemical carcinogenesis involves procarcinogen activation to a genotoxin and induction of mutations in critical genes, many of which favor the growth of initiated cells which, after clonal expansion, eventually give rise to a tumor. Cellular defense mechanisms counteract carcinogenesis at multiple levels e.g. carcinogen metabolism, DNA repair, cell cycle arrest and/or apoptosis (Hengstler et al. 2003). Although these individual steps have been studied intensely over the last decades there are major gaps in our knowledge on how for example species and gender/sex diVerences but also diVerent developmental stages decisively modulate these processes and, in turn, how development and aging is modulated by carcinogens. In a series of consecutive talks the workshop addressed novel aspects in environmental cancer. One focus was on Meeting report of the ECNIS workshop on basic mechanisms of carcinogenesis.