SPELL - Nematode

Citation	Camacho J, de Conti A, Pogribny IP, Sprando RL, Hunt PR. Assessment of the effects of organic vs. inorganic arsenic and mercury in Caenorhabditis elegans. Curr Res Toxicol, 2022.
PubMed ID	35602005
Short Description	Assessment of the effects of organic vs. inorganic arsenic and mercury in Caenorhabditis elegans. GEO Record: GSE196891 Platform: GPL10094 Download gene-centric, log2 transformed data: WBPaper00064061.ce.mr.csv
# of Conditions	16
Full Description	Exposures to mercury and arsenic are known to pose significant threats to human health. Effects specific to organic vs. inorganic forms of these toxic elements are less understood however, especially for organic dimethylarsinic acid (DMA), which has recently been detected in pups of rodent dams orally exposed to inorganic sodium (meta)arsenite (NaAsO2). Caenorhabditis elegans is a small animal alternative toxicity model. To fill data gaps on the effects of DMA relative to NaAsO2, C. elegans were exposed to these two compounds alongside more thoroughly researched inorganic mercury chloride (HgCl2) and organic methylmercury chloride (meHgCl). For timing of developmental milestone acquisition in C. elegans, meHgCl was 2 to 4-fold more toxic than HgCl2, and NaAsO2 was 20-fold more toxic than DMA, ranking the four compounds meHgCl > HgCl2 > NaAsO2 ≫ DMA for developmental toxicity. Methylmercury induced significant decreases in population locomotor activity levels in developing C. elegans. DMA was also associated with developmental hypoactivity, but at >100-fold higher concentrations than meHgCl. Transcriptional alterations in native genes were observed in wild type C. elegans adults exposed to concentrations equitoxic for developmental delay in juveniles. Both forms of arsenic induced genes involved in immune defense and oxidative stress response, while the two mercury species induced proportionally more genes involved in transcriptional regulation. A transgenic bioreporter for activation of conserved proteosome specific unfolded protein response was strongly activated by NaAsO2, but not DMA at tested concentrations. HgCl2 and meHgCl had opposite effects on a bioreporter for unfolded protein response in the endoplasmic reticulum. Presented experiments indicating low toxicity for DMA in C. elegans are consistent with human epidemiologic data correlating higher arsenic methylation capacity with resistance to arsenic toxicity. This work contributes to the understanding of the accuracy and fit-for-use categories for C. elegans toxicity screening and its usefulness to prioritize compounds of concern for further testing. Experimental Details: WBPaper00064061:Water_rep2G WBPaper00064061:NaAsO2_rep2H WBPaper00064061:DMA_rep2I WBPaper00064061:HgCl2_rep2J WBPaper00064061:meHgCl_rep2L WBPaper00064061:Water_rep3F WBPaper00064061:NaAsO2_rep3G WBPaper00064061:DMA_rep3H WBPaper00064061:HgCl2_rep3I WBPaper00064061:meHgCl_rep3J WBPaper00064061:Water_rep4F WBPaper00064061:NaAsO2_rep5G WBPaper00064061:DMA_rep5H WBPaper00064061:HgCl2_rep5I WBPaper00064061:meHgCl_rep5J WBPaper00064061:Water_rep5F.
Tags	Method: microarray, Species: Caenorhabditis elegans, Topic: response to chemical