Integration of toxicological approaches with “omic” and related technologies to elucidate mechanisms of carcinogenic action: Propiconazole, an example

The field of mechanistic chemical carcinogenesis has evolved with the advent and advances in genomic, proteomic and metabolomic technologies. These advances allow mechanistic events along the process of exposure to frank tumors to be studied in great detail. Herein is reviewed an example of this approach using, propiconazole, a triazole-containing antifungal agent that is a mouse hepatocarcinogen. This review will highlight those toxicological, genomic, proteomic and metabolomic findings in mice that were used to describe a set of linked events that lead to propiconazole-induced hepatocarcinogenesis. Independent experimental proof of many of these events is presented that solidified this proposed mechanism of carcinogenic action for propiconazole.

► A mechanism for the hepatocarcinogenic activity of propiconazole has been developed.
► Toxicological and omic (gene and protein expression and metabolomics) data were amalgamated into a cohesive description of the cancer process.
► Independent experimental proof provided a validation of the interpretation of the omic data.
► The relevance of this mechanism of action in mice to humans is discussed.