Biomaterial Database

The effect of toxicokinetics on murine mercury-induced autoimmunity. 1998

P Hultman, and J B Nielsen

Department of Health and Environment, Linköping University, Linköping, Sweden.

Mercury induces autoantibodies to the nucleolar protein fibrillarin (ANoA) in genetically susceptible (H-2AS) mouse strains. This study examines the importance of mercury toxicokinetics for the induction and strength (titer) of these autoantibodies. Female mice of the inbred strains A.SW and B10.S (H-2AS on the A and C57BL/10 genetic background, respectively) and A.TL and B10.TL (H-2Ak on the A and C57BL/10 background) were treated with 203HgCl2 in a dose of 1, 5, or 16 mg Hg/L drinking water for 56-70 days. Whole-body retention of 203Hg was monitored throughout the experimental period. Mercury accumulation in kidney, liver, heart, spleen, and brain was determined at end of the experiment when blood samples were also obtained for determination of ANoA. The drinking water consumption showed a limited variation between the strains and the dose groups. Therefore, intake of mercury did not vary much between the strains at a given dose level. The whole-body retention of mercury reached steady state after 4-5 weeks. In general, the B10.S and B10.TL strains showed a lower whole-body retention and deposition of mercury in the kidney and the liver, compared with the A.SW and A.TL strains given the same dose of mercury. The B10.S strain showed a threshold for induction of ANoA at 5 mg Hg/L, whereas ANoA were still seen in A.SW mice given 1 mg Hg/L. Taken together, this is compatible with a less efficient elimination of mercury in the A.SW and A.TL strains, which was also supported by the higher ratio between whole-body retention and intake of mercury in these strains. These findings indicate that genes residing outside the H-2 (MHC) complex play an important role for regulating mercury toxicokinetics, the A genes conferring higher accumulation of mercury in the body than the B10 genes. In mice congenic with regard to the susceptible H-2AS haplotype, a highly significant correlation (P<0.01) existed between on the one hand the whole-body retention and organ accumulation of mercury and on the other hand the titer of ANoA. We conclude that mercury toxicokinetics differs significantly among inbred mouse strains. The differences in toxicokinetics are regulated by non-H-2 genes and correlate with the autoimmune response in the genetically susceptible strains: quantitatively as the titer of the ANoA and qualitatively as different threshold doses for induction of ANoA by mercury.

UI	MeSH Term	Description	Entries
D008627	Mercuric Chloride	Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant.	Mercury Dichloride,Corrosive Sublimate,HgCl2,Mercuric Perchloride,Mercury Bichloride,Mercury Perchloride,Sublimate,Bichloride, Mercury,Chloride, Mercuric,Dichloride, Mercury,Perchloride, Mercuric,Perchloride, Mercury,Sublimate, Corrosive
D008628	Mercury	A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.
D008631	Mercury Radioisotopes	Unstable isotopes of mercury that decay or disintegrate emitting radiation. Hg atoms with atomic weights 185-195, 197, 203, 205, and 206 are radioactive mercury isotopes.	Radioisotopes, Mercury
D008805	Mice, Inbred A	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	Mouse, Inbred A,Inbred A Mice,Inbred A Mouse
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011834	Radiation Monitoring	The observation, either continuously or at intervals, of the levels of radiation in a given area, generally for the purpose of assuring that they have not exceeded prescribed amounts or, in case of radiation already present in the area, assuring that the levels have returned to those meeting acceptable safety standards.	Monitoring, Radiation
D002868	Chromosomal Proteins, Non-Histone	Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.	Non-Histone Chromosomal Proteins,Chromosomal Proteins, Non Histone,Chromosomal Proteins, Nonhistone,Non-Histone Chromosomal Phosphoproteins,Chromosomal Phosphoproteins, Non-Histone,Non Histone Chromosomal Phosphoproteins,Non Histone Chromosomal Proteins,Nonhistone Chromosomal Proteins,Proteins, Non-Histone Chromosomal
D004198	Disease Susceptibility	A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.	Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D004202	Disinfectants	Substances used on inanimate objects that destroy harmful microorganisms or inhibit their activity. Disinfectants are classed as complete, destroying SPORES as well as vegetative forms of microorganisms, or incomplete, destroying only vegetative forms of the organisms. They are distinguished from ANTISEPTICS, which are local anti-infective agents used on humans and other animals. (From Hawley's Condensed Chemical Dictionary, 11th ed)	Biocide,Disinfectant,Biocides
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response