title: Differential sensitivities of bone marrow, spleen and thymus to genotoxicity induced by environmentally relevant concentrations of arsenite.
abstract: It is known in humans and mouse models, that drinking water exposures to arsenite (As+3) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As+3, and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As+3via drinking water for 30d. Oxidation State Specific Hydride Generation- Cryotrapping- Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA+3) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA+3levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As+3and MMA+3revealed that bone marrow cells are most sensitive to As+3treatment, and MMA+3is more genotoxic than As+3. These results suggest that the differential sensitivities of the three immune organs to As+3exposure are due to the different intracellular arsenic species and concentrations, and that MMA+3may play a critical role in immunotoxicity.
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
authors.forename: Shea
authors.initials: S
authors.lastname: McClain
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Medina
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
authors.forename: Fredine T
authors.initials: FT
authors.lastname: Lauer
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, United States.
authors.forename: Christelle
authors.initials: C
authors.lastname: Douillet
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
authors.forename: Ke Jian
authors.initials: KJ
authors.lastname: Liu
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
authors.forename: Laurie G
authors.initials: LG
authors.lastname: Hudson
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, United States.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Stýblo
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States. Electronic address: sburchiel@salud.unm.edu.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Burchiel
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D018053:Arsenites; D060766:Drinking Water; D009153:Mutagens; D009942:Organometallic Compounds; D014874:Water Pollutants, Chemical; C406082:monomethylarsonous acid; D011065:Poly(ADP-ribose) Polymerases; C015001:arsenite
keywords: Arsenic; Bone marrow; Genotoxicity; Immunotoxicity; Intracellular arsenic species; Spleen; Thymus