a-high-throughput-assay-for-prediction-chemical-toxicity-automated

A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of <em>Caenorhabditis elegans</em>

Applying toxicity testing of chemicals in higher order organisms, such as mice or rats, is time-consuming and expensive, due to their long lifespan and ...

Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research, China

Capital Medical University, China

Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages. One example of such a model is the nematode Caenorhabditis elegans. There are some advantages of C. elegans, such as small size, short life cycle, well defined genome, ease of maintenance and efficient reproduction.

Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans.

In this study, we performed the toxicological assessment of outdoor PM collected from Beijing during Spring Festival using the  assay system of . Acute exposure to outdoor PM at a concentration of 10 mg L and prolonged exposure to outdoor PM at concentrations of 0.1-10 mg L decreased locomotion behavior and caused significant induction of intestinal ROS production. Meanwhile, outdoor PM exposure induced significant expression of gene ( and ) encoded metallothioneins in the intestine. Mutation of the  or  gene resulted in a susceptible property of nematodes to outdoor PM toxicity. Genetic assays suggested that  and  genes acted downstream of the  gene encoding a FOXO transcriptional factor and  gene encoding an insulin receptor in the insulin signaling pathway to regulate outdoor PM toxicity. DAF-2 further acted upstream of DAF-16 and suppressed the function of DAF-16 to regulate outdoor PM toxicity. Therefore, we identified a signaling cascade of DAF-2-DAF-16-MTL-1/2 in the control of outdoor PM toxicity in nematodes. Our study provides an important molecular basis for the potential toxicity of outdoor PM during Spring Festival in Beijing in nematodes. Especially, our study will highlight the potential adverse effects of outdoor PM during Spring Festival on environmental organisms.

Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM) during Spring Festival in Beijing in nematode .

Article	Year
Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans. BMC pharmacology & toxicology\| PubMed ID: 29669598	2018
Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM) during Spring Festival in Beijing in nematode . Toxicology research\| PubMed ID: 30090415	2016

Guojun Li

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