PMID- 25765285
OWN - NLM
STAT- MEDLINE
DCOM- 20170413
LR  - 20170413
IS  - 1477-0393 (Electronic)
IS  - 0748-2337 (Linking)
VI  - 32
IP  - 9
DP  - 2016 Sep
TI  - Low doses of mercuric chloride cause the main features of anti-nucleolar 
      autoimmunity in female outbred CFW mice.
PG  - 1663-74
LID - 10.1177/0748233715573691 [doi]
AB  - The growth of the influence of anthropogenic factors aimed on the improvement of 
      human life has its side effect, for example, living organisms receive increasing 
      exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) 
      salts are able to induce systemic autoimmunity in rodents. This Hg-induced 
      autoimmune process (HgIA) is characterized by T cell-dependent polyclonal 
      activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) 
      and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), 
      and immune complex deposition in multiple organs. HgIA in mice is used as a model 
      of human systemic autoimmune disorders. However, the dose of mercuric chloride 
      (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable 
      limit for everyday levels of Hg exposure in humans. So, we decided to determine 
      the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth 
      Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The 
      lowest dose (50 microg/kg body weight (b.w.)/week) was chosen to match the World 
      Health Organization provisional weekly tolerable intake of total Hg for humans. 
      We also tested HgCl2 at 500 and 1500 microg/kg b.w./week (6.5- and 2-fold less than 
      usually used for induction of HgIA in mice). We found that even the lowest dose 
      of Hg resulted in a statistically significant increase in serum level of IgG1 
      after 8 weeks of treatment. HgCl2 in doses 500 and 1500 microg/kg b.w./week resulted 
      in a significant increase in serum level of IgG1 after 4 weeks of treatment, 
      followed by ANoA production. Sera of HgCl2-treated mice stained the regions in 
      which the major autoantigen in HgIA, fibrillarin, was revealed. These results 
      suggest that low doses of Hg are able to induce the main features of HgIA in 
      genetically heterozygous mice, and that humans chronically exposed to low doses 
      of Hg may be at risk of autoimmunity induction regardless of their genetic 
      background.
CI  - (c) The Author(s) 2015.
FAU - Arefieva, Alla S
AU  - Arefieva AS
AD  - Laboratory of Structural Biochemistry, M.M. Shemyakin-Yu.A. Ovchinnikov Institute 
      of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian 
      Federation quality4@rambler.ru.
FAU - Kamaeva, Alfia G
AU  - Kamaeva AG
AD  - Group of Experimental Biology, M.M. Shemyakin-Yu.A. Ovchinnikov Institute of 
      Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian 
      Federation.
FAU - Krasilshchikova, Marina S
AU  - Krasilshchikova MS
AD  - Group of Experimental Biology, M.M. Shemyakin-Yu.A. Ovchinnikov Institute of 
      Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian 
      Federation.
LA  - eng
PT  - Journal Article
DEP - 20150312
PL  - England
TA  - Toxicol Ind Health
JT  - Toxicology and industrial health
JID - 8602702
RN  - 0 (Antigens, Nuclear)
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Immunoglobulin G)
RN  - 0 (fibrillarin)
RN  - 53GH7MZT1R (Mercuric Chloride)
SB  - IM
MH  - Animals
MH  - Animals, Outbred Strains
MH  - Antigens, Nuclear/*metabolism
MH  - Autoantibodies/analysis/biosynthesis
MH  - Autoantigens/metabolism
MH  - Autoimmune Diseases/*etiology
MH  - Autoimmunity/*drug effects
MH  - Cell Nucleolus/*drug effects/immunology/metabolism/pathology
MH  - Chromosomal Proteins, Non-Histone/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Environmental Pollutants/administration & dosage/*toxicity
MH  - Female
MH  - Immunoglobulin G/analysis
MH  - Injections, Subcutaneous
MH  - Mercuric Chloride/administration & dosage/*toxicity
MH  - Mercury Poisoning/blood/immunology/pathology/*physiopathology
MH  - Mice
MH  - Organ Size/drug effects
MH  - Specific Pathogen-Free Organisms
MH  - Spleen/drug effects/immunology/metabolism/pathology
OTO - NOTNLM
OT  - Low doses
OT  - PTWI
OT  - antinucleolar autoantibodies
OT  - autoimmune process
OT  - mercuric chloride
OT  - outbred mice
EDAT- 2015/03/15 06:00
MHDA- 2017/04/14 06:00
CRDT- 2015/03/14 06:00
PHST- 2015/03/14 06:00 [entrez]
PHST- 2015/03/15 06:00 [pubmed]
PHST- 2017/04/14 06:00 [medline]
AID - 0748233715573691 [pii]
AID - 10.1177/0748233715573691 [doi]
PST - ppublish
SO  - Toxicol Ind Health. 2016 Sep;32(9):1663-74. doi: 10.1177/0748233715573691. Epub 
      2015 Mar 12.