Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

Journal Article · Tue Dec 15 04:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.09.019· OSTI ID:21344807

Mitchell, Leah A; Lauer, Fredine T; Xi, Sun ^[1]; McDonald, Jacob D ^[2]; Hudson, Laurie G; Kejian, Liu ^[1]

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1. Toxicology and Pharmaceutical Sciences Program, University of New Mexico College of Pharmacy, Albuquerque, NM 87131 (United States)
2. Lovelace Respiratory Research Institute, Albuquerque, NM 87109 (United States)

In these studies the immunotoxicity of arsenic trioxide (ATO, As{sub 2}O{sub 3}) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 mug/m{sup 3} and 1 mg/m{sup 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 mug/g tissue following the 1 mg/m{sup 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 mug/m{sup 3} and 1 mg/m{sup 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.

• OSTI ID: 21344807
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 241; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
ANIMALS
ANTIBODIES
ARSENATES
ARSENIC COMPOUNDS
ARSENIC OXIDES
BIOLOGICAL MATERIALS
BLADDER
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHALCOGENIDES
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
FACE
GLANDS
HEAD
INHALATION
INHIBITION
INTAKE
KIDNEYS
LEUKOCYTES
LIVER
LUNGS
LYSIS
MACROPHAGES
MAMMALS
MATERIALS
MICE
NATURAL KILLER CELLS
NOSE
ORGANS
OXIDES
OXYGEN COMPOUNDS
PHAGOCYTES
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
SPLEEN
SPLEEN CELLS
TOXICITY
URINARY TRACT
VERTEBRATES