| Citation | Gong P, Donohue KB, Mayo AM, Wang Y, Hong H, Wilbanks MS, Barker ND, Guan X, Gust KA. Comparative toxicogenomics of three insensitive munitions constituents 2,4-dinitroanisole, nitroguanidine and nitrotriazolone in the soil nematode Caenorhabditis elegans. BMC Syst Biol, 2018. |
| PubMed ID | 30547801 |
| Short Description | Comparative toxicogenomics of three insensitive munitions constituents 2,4-dinitroanisole, nitroguanidine and nitrotriazolone in the soil nematode Caenorhabditis elegans. GEO Record: GSE92365 Platform: GPL22795 Download gene-centric, log2 transformed data: WBPaper00055899.ce.mr.csv |
| # of Conditions | 48 |
Full Description
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BACKGROUND: Ecotoxicological studies on the insensitive munitions formulation IMX-101 and its components 2,4-dinitroanisole (DNAN), nitroguanidine (NQ) and nitrotriazolone (NTO) in various organisms showed that DNAN was the main contributor to the overall toxicity of IMX-101 and suggested that the three compounds acted independently. These results motivated this toxicogenomics study to discern toxicological mechanisms for these compounds at the molecular level. METHODS: Here we used the soil nematode Caenorhabditis elegans, a well-characterized genomics model, as the test organism and a species-specific, transcriptome-wide 44K-oligo probe microarray for gene expression analysis. In addition to the control treatment, C. elegans were exposed for 24h to 6 concentrations of DNAN (1.95-62.5ppm) or NQ (83-2667ppm) or 5 concentrations of NTO (187-3000ppm) with ten replicates per treatment. The nematodes were transferred to a clean environment after exposure. Reproduction endpoints (egg and larvae counts) were measured at three time points (i.e., 24-, 48- and 72-h). Gene expression profiling was performed immediately after 24-h exposure to each chemical at the lowest, medium and highest concentrations plus the control with four replicates per treatment. RESULTS: Statistical analyses indicated that chemical treatment did not significantly affect nematode reproduction but did induce 2175, 378, and 118 differentially expressed genes (DEGs) in NQ-, DNAN-, and NTO-treated nematodes, respectively. Bioinformatic analysis indicated that the three compounds shared both DEGs and DEG-mapped Reactome pathways. Gene set enrichment analysis further demonstrated that DNAN and NTO significantly altered 12 and 6 KEGG pathways, separately, with three pathways in common. NTO mainly affected carbohydrate, amino acid and xenobiotics metabolism while DNAN disrupted protein processing, ABC transporters and several signal transduction pathways. NQ-induced DEGs were mapped to a wide variety of metabolism, cell cycle, immune system and extracellular matrix organization pathways. CONCLUSION: Despite the absence of significant effects on apical reproduction endpoints, DNAN, NTO and NQ caused significant alterations in gene expression and pathways at 1.95ppm, 187ppm and 83ppm, respectively. This study provided supporting evidence that the three chemicals may exert independent toxicity by acting on distinct molecular targets and pathways. Experimental Details: WBPaper00055899:NTO_Control_rep5 WBPaper00055899:NTO_187ppm_rep5 WBPaper00055899:DNAN_Control_rep3 WBPaper00055899:DNAN_15.5ppm_rep1 WBPaper00055899:DNAN_1.9ppm_rep1 WBPaper00055899:DNAN_62.5ppm_rep3 WBPaper00055899:NTO_3000ppm_rep4 WBPaper00055899:NQ_Control_rep1 WBPaper00055899:NQ_83ppm_rep2 WBPaper00055899:NTO_750ppm_rep3 WBPaper00055899:NTO_3000ppm_rep5 WBPaper00055899:DNAN_62.5ppm_rep1 WBPaper00055899:DNAN_1.9ppm_rep5 WBPaper00055899:NQ_666ppm_rep4 WBPaper00055899:NQ_83ppm_rep1 WBPaper00055899:DNAN_15.5ppm_rep2 WBPaper00055899:NQ_666ppm_rep1 WBPaper00055899:NTO_3000ppm_rep1 WBPaper00055899:NQ_2667ppm_rep4 WBPaper00055899:DNAN_15.5ppm_rep4 WBPaper00055899:DNAN_15.5ppm_rep5 WBPaper00055899:NTO_187ppm_rep3 WBPaper00055899:NQ_666ppm_rep5 WBPaper00055899:NQ_2667ppm_rep3 WBPaper00055899:NQ_83ppm_rep5 WBPaper00055899:DNAN_62.5ppm_rep4 WBPaper00055899:NQ_2667ppm_rep2 WBPaper00055899:NTO_750ppm_rep5 WBPaper00055899:DNAN_Control_rep1 WBPaper00055899:NTO_Control_rep1 WBPaper00055899:DNAN_Control_rep2 WBPaper00055899:NQ_666ppm_rep2 WBPaper00055899:DNAN_1.9ppm_rep2 WBPaper00055899:DNAN_62.5ppm_rep5 WBPaper00055899:DNAN_Control_rep4 WBPaper00055899:DNAN_1.9ppm_rep3 WBPaper00055899:NQ_Control_rep3 WBPaper00055899:NTO_Control_rep3 WBPaper00055899:NQ_83ppm_rep4 WBPaper00055899:NTO_750ppm_rep1 WBPaper00055899:NQ_Control_rep2 WBPaper00055899:NTO_187ppm_rep1 WBPaper00055899:NTO_3000ppm_rep2 WBPaper00055899:NQ_2667ppm_rep1 WBPaper00055899:NTO_187ppm_rep4 WBPaper00055899:NTO_Control_rep2 WBPaper00055899:NTO_750ppm_rep4 WBPaper00055899:NQ_Control_rep4. |
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