Differential expression of genes in C. elegans reveals transcriptional responses to indirect-acting xenobiotic compounds and insensitivity to 2,3,7,8-tetrachlorodibenzodioxin

Caenorhabditis elegans is a well-established model organism for toxicity testing of chemical substances. We recently demonstrated its potential for bioanalysis of the toxic potency of chemical contaminants in water. While many detoxification genes are homologues to those in mammalians, C. elegans is reported to be deficient in cytochrome CYP1-like P450 metabolism and that its aryl hydrocarbon receptor (AhR) homolog encoded by ahr-1 purportedly does not interact with dioxins or any other known xenobiotic ligand. This suggests that C. elegans is insensitive for compounds that require bioactivation (indirectly acting compounds) and for dioxins or dioxin-like compounds. This study analysed genome-wide gene expression of the nematode in response to 30 mu M of aflatoxin B1 (AFB1), benzo(a)pyrene (B(a)P), Aroclor 1254 (PCB1254), and 10 mu M of 2,3,7,8-tetrachlorodibenzodioxin (TCDD). After 24 h of exposure in the early L4 larval stage, microarray analysis revealed 182, 86, and 321 differentially expressed genes in the nematodes treated with 30 mu M of AFB1, B(a)P, and PCB1254, respectively. Among these genes, many encode xenobiotic-metabolizing enzymes, and their transcription levels were among the highest-ranked fold-changed genes. Interestingly, only one gene (F59B1.8) was upregulated in the nematodes exposed to 10 mu M TCDD. Genes related to metabolic processes and catalytic activity were the most induced by exposure to 30 mu M of AFB1, B(a)P, and PCB1254. Despite the genotoxic nature of AFB1 and B(a)P, no differential expression was found in the genes encoding DNA repair and cell cycle checkpoint proteins. Analysis of con-centration-response curves was performed to determine the Lowest Observed Transcriptomic Effect Levels (LOTEL) of AFB1, B(a)P, and PCB1254. The obtained LOTEL values showed that gene expression changes in C. elegans are more sensitive to toxicants than reproductive effects. Overall, transcriptional responses of meta-bolic enzymes suggest that the nematode does metabolize AFB1, B(a)P, and PCB1254. Our findings also support the assumption that the transcription factor AhR homolog in C. elegans does not bind typical xenobiotic ligands, rendering the nematode transcriptionally insensitive to TCDD effects.

Automated summary

This study found that Caenorhabditis elegans is sensitive to gene expression changes induced by AFB1, B(a)P, and PCB1254, but insensitive to TCDD effects. Despite the absence of differential expression in genes encoding DNA repair and cell cycle checkpoint proteins, the transcriptional responses of metabolic enzymes suggest that the nematode is capable of metabolizing AFB1, B(a)P, and PCB1254.