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GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE
Citation:
Rosen, M B., V S. Wilson, J E. Schmid, AND L E. Gray Jr. GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
GENE ARRAY ANALYSIS OF THE VENTRAL PROSTATE IN RATS EXPOSED TO EITHER VINCLOZOLIN OR PROCYMIDONE. MB Rosen, VS Wilson, JE Schmid, and LE Gray Jr. US EPA, ORD, NHEERL, RTP, NC.
Vinclozolin (Vi) and procymidone (Pr) are antiandrogenic fungicides. While changes in gene expression have been described in the ventral prostate (VP) following vinclozolin exposure, similar studies have not been conducted with procymidone, a compound proposed to share a common mechanism of action (see VS Wilson et al., SOT 2003). Here we examine the gene expression profiles of animals exposed to both compounds. 100 day old male SD rats were surgically castrated and administered silastic implants either with or without testosterone. A subset of testosterone treated animals were then orally dosed using 200 mg/kg of either vinclozolin or procymidone in corn oil. Four treatment groups with six animals per group were utilized: castrated (C), testosterone (T), testosterone+Vi (V), and testosterone+Pr (P). Tissue from the VP was collected from 3 animals per group at 20 hrs and 4 days after the start of treatment for isolation of total RNA followed by analysis using Clontech Atlas 1.2 Toxicology arrays. In support of the hypothesis that Pr shares a common mechanism or mode of action with Vi, similar changes in gene expression were observed in the C, P and V groups at both the 20 hr and 4 day time points. While only 36 genes were affected at 20 hrs, 156 genes were altered 4 days after the start of treatment. This may in part reflect regression of the VP at the later time point. Of note was an up-regulation of the androgen receptor after 20 hrs of treatment along with an up-regulation of clusterin after 4 days. Both changes were predicted in the C, P and T groups prior to the conduct of the study. Of interest for future studies is the kallikrein family of serine proteases which appeared to be a more robust marker of androgenic activity than clusterin. The effects of Vi after 4 days of treatment were, in a number of cases, greater than those of procymidone, suggesting that vinclozolin may be a more potent antiandrogen than Pr. A replicate of this study is currently being conducted. This abstract does not necessarily reflect EPA policy.