Gene expression profiling of oxidative genotoxic compounds in hepatocarcinogenesis
Hepatocellular carcinoma (HCC) is one of the most common visceral neoplasms in the world. Although Hepatitis B and C virus infection constitute app. 80% of the major risk factors for HCC, other risk factors include exposure to compounds present in diet and cigarette smoke. Increased production of ROS (oxidative stress) induced by these compounds or metabolites plays an important role in hepatocarcinogenesis. Furthermore, the oxidative stress related mechanism of HCC seems to be associated with intrinsic drug resistance. A specific oxidative genotoxic gene expression profile will be developed, and will be used for following objectives:
- Identification of the genotoxic mechanisms underlying the mechanism of HCC and associated intrinsic drug resistance are of primary importance for new approaches to liver cancer prevention and treatment and
- Identification of a set of genes that ca be used as a biomarker for the development of a high-throughput screen for the identification of (new) oxidative genotoxic compounds in hepatocarcinogenesis.