You are here:
COMPARISON OF GENE EXPRESSION PROFILES FROM RATS FED THREE TOXICOLOGICALLY DIFFERENT CONAZOLES
Citation:
Hester, S D., S. F. Thai, D C. Wolf, E. Winkfield, W. O. Ward, AND S. C. Nesnow. COMPARISON OF GENE EXPRESSION PROFILES FROM RATS FED THREE TOXICOLOGICALLY DIFFERENT CONAZOLES. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Conazoles arc a class of fungicides used as pharmaceutical and agricultural products. In chronic bioassays, triadimefon was hepatotoxic and induced transitional cell adenomas in the thyroid gland. Both propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. It has been proposed that triadimefon induces thyroid tumors by altering the levels of thyroid hormone and TSH as a result of induction of xenobiotic metabolizing enzymes. Genomic profiling was utilized to investigate whether transcriptional alterations were associated with their toxic mode of action. Male Wistar rats (3 per group) were exposed to conazoles in the feed for 4 days: triadimefon (1800 ppm), propiconazole (2500 ppm), myclobutanil (2000 ppm). Hepatic gene expression was performed using Affymetrix GeneChips (Rat 230_2). Differential gene expression was assessed at the probe level using Robust Multichip Average Analysis (RMA). De Novo gene expression between treatment groups was analyzed using hierarchical clustering, K-Nearest Neighbor, and PCA. All 3 conazoles could be discriminated from controls with propiconazole and myclobutanil clustering together and distinct from triadimefon. Statistical analyses showed 150 genes were in common among the 3 conazoles including several cytochromes P450s, GSTs, and one UDPglucuronosyltransferase. In contrast, 500 genes were unique to triadimefon. These genes were mapped to several gene networks including steroid biosynthesis, cell proliferation, and DNA repair pathways. Future analyses will focus on associating these alterations with triadimefon's toxicological effects.