Assessment of the effects of organic vs. inorganic arsenic and mercury in Caenorhabditis elegans

Camacho, Jessica; Conti, Aline de; Pogribny, Igor P.; Sprando, Robert L.; Hunt, Piper Reid

doi:10.1016/j.crtox.2022.100071

Cited by 13 publications

(15 citation statements)

References 157 publications

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“…In a previous study, approximately 20‐fold higher concentrations of organic DMA relative to inorganic NaAsO 2 were required to induce similar effects on developmental timing in juveniles and gene expression in adults (Camacho et al, 2022). In that study, the juvenile LOELs for changes in SLA for NaAsO 2 and DMA were 10 and 300 μg/mL, respectively.…”

Section: Discussionmentioning

confidence: 93%

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The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans

Hunt

Welch

Camacho

et al. 2023

J of Applied Toxicology

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We have adapted a semiautomated method for tracking Caenorhabditis elegans spontaneous locomotor activity into a quantifiable assay by developing a sophisticated method for analyzing the time course of measured activity. The 16‐h worm Adult Activity Test (wAAT) can be used to measure C. elegans activity levels for efficient screening for pharmacological and toxicity‐induced effects. As with any apical endpoint assay, the wAAT is mode of action agnostic, allowing for detection of effects from a broad spectrum of response pathways. With caffeine as a model mild stimulant, the wAAT showed transient hyperactivity followed by reversion to baseline. Mercury chloride (HgCl2) produced an early dose–response hyperactivity phase followed by pronounced hypoactivity, a behavior pattern we have termed a toxicant “escape response.” Methylmercury chloride (meHgCl) produced a similar pattern to HgCl2, but at much lower concentrations, a weaker hyperactivity response, and more pronounced hypoactivity. Sodium arsenite (NaAsO2) and dimethylarsinic acid (DMA) induced hypoactivity at high concentrations. Acute toxicity, as measured by hypoactivity in C. elegans adults, was ranked: meHgCl > HgCl2 > NaAsO2 = DMA. Caffeine was not toxic with the wAAT at tested concentrations. Methods for conducting the wAAT are described, along with instructions for preparing C. elegans Habitation Medium, a liquid nutrient medium that allows for developmental timing equivalent to that found with C. elegans grown on agar with OP50 Escherichia coli feeder cultures. A de novo mathematical parametric model for adult C. elegans activity and the application of this model in ranking exposure toxicity are presented.

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Section: Discussionmentioning

confidence: 93%

“…Human neurotoxicants mercury chloride (HgCl 2 ), methylmercury chloride (meHgCl), and sodium arsenite (NaAsO 2 ) were used as positive controls for inducing behavior changes in C. elegans (Camacho et al, 2022; McElwee & Freedman, 2011; Yu & Liao, 2014). Caffeine (Caff) was used as a control for mild stimulant effects.…”

Section: Introductionmentioning

confidence: 99%

The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans

Hunt

Welch

Camacho

et al. 2023

J of Applied Toxicology

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“…It should be noted that the concentration of sodium arsenite was lower than that of dimethylarsenic acid to perform similar effects; sodium arsenite at 25 µM for 24 h treatment significantly reduced cell viability to 53%, while dimethylarsenic acid 25 mM for 24 h treatment was needed to reduce OC3 cell viability to 49% in MTT cell viability test. It is known that inorganic arsenic compounds are more toxic than organic arsenic compounds ( 3 , 4 , 42 ). Inorganic arsenic compounds can be methylated to become less toxic compounds processed by methyltransferases in liver, a detoxification reaction, and the methylation occurs through alternating reductive and oxidative methylation reactions ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Sodium arsenite and dimethylarsenic acid induces apoptosis in OC3 oral cavity cancer cells

Lan

Chu

et al. 2022

Mol Med Rep

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although arsenic is an environmental toxicant, arsenic trioxide (aTo) is used to treat acute promyelocytic leukemia (aPl) with anticancer effects. Studies have demonstrated oral cancer is in the top 10 cancers in Taiwan. High rate of oral cancers is linked to various behaviors, such as excessive alcohol consumption and tobacco use. Similarly, betel chewing is a strong risk factor in oral cancer. in the present study, oral squamous carcinoma oc3 cells were investigated with the treatments of sodium arsenite (naaso 2 ) and dimethylarsenic acid (dMa), respectively, to examine if arsenic compounds have anti-cancer efforts. it was found that 1 µM naaso 2 and 1 mM dMa for 24 h induced rounded contours with membrane blebbing phenomena in oc3 cells, revealing cell apoptotic characteristics. in addition, naaso 2 (10-100 µM) and DMA (1-100 mM) significantly decreased OC3 cell survival. In cell cycle regulation detected by flow cytometry, NaAsO 2 and DMA significantly augmented percentage of subG 1 and G 2 /M phases in oc3 cells, respectively. annexin V/Pi double staining assay was further used to confirm NaAsO 2 and dMa did induce oc3 cell apoptosis. in mechanism investigation, western blotting assay was applied and the results showed that naaso 2 and DMA significantly induced phosphorylation of JnK, erK1/2 and p38 and then the cleavages of caspase-8, -9, -3 and poly adP-ribose polymerase (ParP) in oc3 cells, dynamically. in conclusion, naaso 2 and dMa activated MaPK pathways and then apoptotic pathways to induce oc3 oral cancer cell apoptosis.

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“…Low-cost maintenance, easy cultivation, and efficient reproduction make this nematode suitable for rapid developmental toxicity testing. C. elegans assays were first used as a biological model and in environmental and chemical toxicity to obtain data from a whole animal with active digestive, reproductive, sensory, and neuromuscular systems 110 , 111 . Nowadays, this model is used in drug toxicity analysis, such as cisplatin 112 and aesculin, a coumarin compound extracted from TCM Qinpi (Cortex Fraxini) 113 .…”

Section: Application Of Biotechnology In Pharmaceutical Products Anal...mentioning

confidence: 99%

Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses

Chen

Zhang

et al. 2022

Acta Pharmaceutica Sinica B

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Assessment of the effects of organic vs. inorganic arsenic and mercury in Caenorhabditis elegans

Cited by 13 publications

References 157 publications

The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans

The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans

Sodium arsenite and dimethylarsenic acid induces apoptosis in OC3 oral cavity cancer cells

Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses

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