System Toxicology Approaches for Evaluating Chemical Carcinogenicity

Abstract

The recent progress in sequencing, genomic technologies and system biological tools has enabled interrogating cellular responses of the whole genome to toxic stimuli via monitoring gene expression profiles and evaluating toxic effects in context of molecular pathways. The feasibility of using “fingerprints” to delineate molecular networks associated with toxicity has also been demonstrated by applying functional genomic approaches that utilized collection of yeast mutants or cancer cell lines. The potential of toxicogenomic analysis for analysis of genotoxic mechanisms to facilitate risk assessment of genotoxicity findings in in vitro assay systems has been extensively discussed. In this review, we focus on discussing recent progress in investigating genotoxic and carcinogenic mechanisms via gene expression profile analysis in in vitro and in vivo assay systems. Furthermore, we provide a perspective on potential application of toxicogenomic analysis as a tool for hazard identification and risk assessment of genotoxic and carcinogenic properties of chemicals. Keywords: genotoxic carcinogens; genotoxicity in vitro; mechanistic toxicogenomics; non-genotoxic carcinogens