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Toxicol Sci. 2012 May;127(1):54-65. doi: 10.1093/toxsci/kfs086. Epub 2012 Feb 14.

The hepatocarcinogenic conazoles: cyproconazole, epoxiconazole, and propiconazole induce a common set of toxicological and transcriptional responses.

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Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.


Conazoles are fungicides used as agricultural pesticides and pharmaceutical products. We investigated whether a common core of toxicological and transcriptional responses underlies the observed carcinogenic effects of three conazoles: cyproconazole, epoxiconazole, and propiconazole. In studies where mice were fed diets of these conazoles for 30 days, we found a common set of toxicological effects altered by these conazoles: hepatomegaly, hepatocellular hypertrophy, decreased serum cholesterol, decreased hepatic levels of all-trans-retinoic acid, and increased hepatic cell proliferation. Microarray-based transcriptional analysis revealed 330 significantly altered probe sets common to these conazoles, many of which showed strong dose responses for cytochrome P450, glutathione S-transferase, and oxidative stress genes. More detailed analyses identified a subset of 80 altered genes common to the three conazoles that were associated with cancer. Pathways associated with these genes included xenobiotic metabolism, oxidative stress, cell signaling, and cell proliferation. A common TGFα-centric pathway was identified within the 80-gene set, which, in combination with the toxicological and other transcriptomic findings, provides a more refined toxicity profile for these carcinogenic conazoles.

[Indexed for MEDLINE]

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