Chemical Safety and Cancer Prevention

(Head: Gergely Szakacz, Prof. Dr.)

Chemical compounds are the dominant cause of human cancer. The focus of our research unit is to elucidate how cancer is induced by chemicals. Improved mechanistic understanding of these complex steps provides targets for prevention and therapy, and biomarkers of exposure and disease. We characterize the effects of mutagenic/genotoxic and non-genotoxic carcinogens on cultured cells, intact organs, and cancer prestages at the cellular and molecular level and also strive for knowledge-based advances in prevention of carcinogenesis by chemical compounds (chemoprevention).

Liver cancer is the third most frequent cause of cancer death worldwide. Our research unit places emphasis on chemical hepatocarcinogenesis and thorough investigations on the single steps of this complex process. After application of genotoxic carcinogens single preneoplastic rat hepatocytes appear (A, in brown), which may give rise to large preneoplasia (in B) and to liver cancer. To enable investigations on the molecular and biological alterations associated with the preneoplastic phenotype, we developed an ex-vivo co-culture system for unaltered and initiated hepatocytes (in C). In these models we identify non-genotoxic carcinogens that promote the outgrowth of initiated hepatocytes to frank malignancy and chemopreventive agents which interfere with this process.