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A microRNA signature for tumorigenic conazoles in mouse liver.
Citation:
ROSS, J. A., S. Thai, M. J. KOHAN, C. I. Jones, T. Chen, AND C. F. BLACKMAN. A microRNA signature for tumorigenic conazoles in mouse liver. Presented at Environmental Mutagenesis Society, St Louis, MO, October 25, 2009.
Impact/Purpose:
This study represents the first identification ofa microRNA signature that differentiates tumorigenic from nonturnorigenic conazoles.
Description:
Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumorigenicity, we analyzed the microRNA expression levels in control and conazole treated mice after 90 days of administration in feed. MicroRNAs (miRI'JAs) are small non-coding RNAs composed of approximately 19-24 nucleotides in length, and have been shown to interact with mRNA (usually 3' UTR) to suppress its expression. miRNAs playa key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Groups of mice were fed either control diet or diet containing 1800 p.p.m. triadimefon, 2500 p.p.m. propiconazole or 2000 p.p.m. myclobutanil. MicroRNA was isolated from livers and analyzed using Superarray whole mouse genome miRNA PCR arrays from SABioscience. Data were analyzed using the Significance Analysis of Microarrays (SAM) procedure. We identified those miRNAs whose expression was either increased or decreased relative to untreated controls with q s 0.01. The tumorigenic conazoles induced many more changes in miRNA expression than the non-tumorigenic conazole. A group of 19 miRNAs was identified whose expression was altered in both triadimefon and propiconazole treated animals but not in myclobutanil treated animals. All but one of the altered miRNAs were downregulated compared to controls. This pattern of altered miRNA expression represents a signature for tumorigenic conazole exposure in mouse liver after 90 days of treatment. This abstract does not reflect US EPA policy.