Comparative toxicogenomic responses of mercuric and methyl-mercury.

BACKGROUND

Mercury is a ubiquitous environmental toxicant that exists in multiple chemical forms. A paucity of information exists regarding the differences or similarities by which different mercurials act at the molecular level.

RESULTS

Transcriptomes of mixed-stage C. elegans following equitoxic sub-, low- and high-toxicity exposures to inorganic mercuric chloride (HgCl2) and organic methylmercury chloride (MeHgCl) were analyzed. In C. elegans, the mercurials had highly different effects on transcription, with MeHgCl affecting the expression of significantly more genes than HgCl2. Bioinformatics analysis indicated that inorganic and organic mercurials affected different biological processes. RNAi identified 18 genes that were important in C. elegans response to mercurial exposure, although only two of these genes responded to both mercurials. To determine if the responses observed in C. elegans were evolutionarily conserved, the two mercurials were investigated in human neuroblastoma (SK-N-SH), hepatocellular carcinoma (HepG2) and embryonic kidney (HEK293) cells. The human homologs of the affected C. elegans genes were then used to test the effects on gene expression and cell viability after using siRNA during HgCl2 and MeHgCl exposure. As was observed with C. elegans, exposure to the HgCl2 and MeHgCl had different effects on gene expression, and different genes were important in the cellular response to the two mercurials.

CONCLUSIONS

These results suggest that, contrary to previous reports, inorganic and organic mercurials have different mechanisms of toxicity. The two mercurials induced disparate effects on gene expression, and different genes were important in protecting the organism from mercurial toxicity.