You are here:
PROPICONAZOLE-INDUCED CARCINOGENESIS: ROLE OF OXIDATIVE STRESS
Citation:
BRUNO, M. E., P. CHEN, T. MOORE, S. NESNOW, AND Y. GE. PROPICONAZOLE-INDUCED CARCINOGENESIS: ROLE OF OXIDATIVE STRESS. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
In order to unravel the toxic processes involved in carcinogenesis as well as to obtain insight into molecular basis and mode of action of propiconazole-induced tumorigenesis, we have performed a genomic analysis of propiconazole-treated mouse livers using cDNA arrays.
Description:
Propiconazole is a systemic foliar fungicide with a broad range of activity. Rodents fed with propiconazole at high dose resulted in diminished body weight, increased liver weight of adults and pups, and eventually liver carcinogenesis. In order to unravel the toxic processes involved in carcinogenesis as well as to obtain insight into molecular basis and mode of action of propiconazole-induced tumorigenesis, we have performed a genomic analysis of propiconazole-treated mouse livers using cDNA arrays. Some important differentially expressed genes and pathways involved in oxidative stress have been identified, suggesting the roles of oxidative stress in propiconazole-induced carcinogenesis. To get a better understanding of oxidative-stress mediated toxicity or carcinogenesis, we have recently developed an integrated proteomic technology platform for analysis of oxidative stress status, antioxidant ability, protein oxidation and identification of biomarkers of oxidative stress during propiconazole-induced carcinogenesis. As the first step, we performed systematic assays for the measurement of antioxidant enzymatic activities of superoxide dismutase, catalase, glutathione s-transferase, GSH/GSSG ratio, total thiol and carbonyl content of proteins in mouse liver tissues treated with propiconazole for four days. A significant decrease in GSH/GSSG ratio, and an increase in carbonyl content and glutathione s-transferase activity in propiconazole-treated mouse livers were observed. To our knowledge, these results may be the first and direct proteomic evidence about involvement and roles of oxidative stress in propiconazole-induced carcinogenesis. In addition, oxidative stress activated carcinogenesis pathways and toxic mechanisms of propiconazole are under investigation.