title: Integration of toxicological approaches with "omic" and related technologies to elucidate mechanisms of carcinogenic action: propiconazole, an example.
abstract: 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.
authors.affiliation: 105 Lonebrook Drive, Chapel Hill, NC 27516, USA. Electronic address: snesnow@pobox.com.
authors.forename: Stephen
authors.initials: S
authors.lastname: Nesnow
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D025461:Feedback, Physiological; D023281:Genomics / Q000379:methods*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D055442:Metabolome; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014116:Toxicology / Q000379:methods*; D014212:Tretinoin / Q000378:metabolism; D014230:Triazoles / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D017382:Reactive Oxygen Species; D014230:Triazoles; C045950:propiconazole; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol