Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure.
In these studies the immunotoxicity of arsenic trioxide (ATO, As(2)O(3)) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 microg/m(3) and 1 mg/m(3). A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 microg/g tissue following the 1 mg/m(3) exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 microg/m(3) and 1 mg/m(3) exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.
Toxicology and Pharmaceutical Sciences Program, The University of New Mexico College of Pharmacy, Albuquerque, NM 87131, USA. Sburchiel@salud.unm.edu
Scott W
SW
Burchiel
Leah A
LA
Mitchell
Fredine T
FT
Lauer
Xi
X
Sun
Jacob D
JD
McDonald
Laurie G
LG
Hudson
Ke Jian
KJ
Liu
D000336:Aerosols; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001151:Arsenic / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006462:Hemolytic Plaque Technique; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000633:toxicity; D007202:Indicators and Reagents; D019570:Inhalation Exposure; D007694:Killer Cells, Natural / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014018:Tissue Distribution
D000336:Aerosols; D001152:Arsenicals; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D008934:Mitogens; D010087:Oxides; D011956:Receptors, Cell Surface; D001151:Arsenic; D000077237:Arsenic Trioxide