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Transcriptomic signatures indicative of a non-genotoxic adverse outcome pathway for small intestine cancer in the duodenum of mice exposed to hexavalent chromium, captan, or folpet

ABSTRACT: We evaluated duodenal tissues of B6C3F1 mice exposed to either Cr(VI) (180ppm in drinking water), captan (≤12000ppm in diet), or folpet (≤16000ppm in diet) for 28 days. TempO-Seq technology was used to measure the sentinel geneset, S1500+, representing ~3000 toxicology-relevant genes. Global exposure-induced transcriptional responses were similar between agents (all Pearson correlation coefficients ≥0.61). Focusing on responses at doses of captan and folpet that correlate most closely with effects of Cr(VI), a gene-level comparison identified that 126/546 (23%) differentially expressed genes were altered in the same direction across all three agents. Pathway-level comparisons identified 25 up-regulated pathways commonly modulated between Cr(VI), captan, and folpet. Commonly altered genes and pathways were related to cellular metabolism, stress, immune response, and cell proliferation. No up-regulated pathways relevant to genotoxicity were associated with responses to any agent.

ORGANISM(S): Mus musculus

PROVIDER: GSE120146 | GEO | 2019/09/18

REPOSITORIES: GEO

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