Expression of metallothionein mRNAs on mouse cerebellum microglia cells by thimerosal and its metabolites

Toxicology. 2009 Jun 30;261(1-2):25-32. doi: 10.1016/j.tox.2009.04.037. Epub 2009 Apr 19.


Effects of thimerosal and its metabolites, ethyl mercury and thiosalicylate, on the expression of metallothionein (MT) mRNAs in mouse cerebellum microglia cell line, C8-B4 cells, were studied. The level of MT-1 mRNA significantly decreased at early hours and recovered time-dependently 24h after thimerosal was added to the C8-B4 cells. However, MT-2 and MT-3 mRNA expressions did not change from the control group. In contrast, the expression of MT-1 mRNA increased in a mouse neuroblastoma cell line 6h after incubation with thimerosal. In addition, the level of MT-1 mRNA decreased in C8-B4 cells 6h after the addition of thiosalicylate, but ethyl mercury induced MT-1 mRNA expression. When cell viability was compared with thimerosal, thiosalicylate, and ethyl mercury, the viability of C8-B4 cells decreased dose-dependently 24h after either thimerosal or ethyl mercury was added; however, the viability increased dose-dependently until 15 microM thiosalicylate was added. From the present results, it is concluded that the expression of MT-1 mRNA may be mediated by different factors than the expression of MT-2 mRNA in C8-B4 cells. The reduction of MT-1 mRNA level by thiosalicylate may affect the proliferation of C8-B4 cells.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biotransformation
  • Cell Line
  • Cell Survival / drug effects
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Cerebellum / pathology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein
  • Metallothionein / genetics*
  • Metallothionein 3
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Nerve Tissue Proteins / genetics
  • Preservatives, Pharmaceutical / metabolism
  • Preservatives, Pharmaceutical / toxicity*
  • RNA, Messenger / metabolism*
  • Rats
  • Salicylates / metabolism
  • Salicylates / toxicity*
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Compounds / toxicity*
  • Thimerosal / metabolism
  • Thimerosal / toxicity*
  • Time Factors
  • Vascular Endothelial Growth Factor A / genetics
  • alpha-Fetoproteins / genetics


  • Glial Fibrillary Acidic Protein
  • Metallothionein 3
  • Mt2 protein, mouse
  • Mt3 protein, mouse
  • Nerve Tissue Proteins
  • Preservatives, Pharmaceutical
  • RNA, Messenger
  • Salicylates
  • Sulfhydryl Compounds
  • Vascular Endothelial Growth Factor A
  • alpha-Fetoproteins
  • glial fibrillary astrocytic protein, mouse
  • metallothionein-1, mouse
  • vascular endothelial growth factor A, mouse
  • Thimerosal
  • Metallothionein
  • thiosalicylic acid