Document 0918
 DOCN  M9540918
 TI    Inhalation exposure to isobutyl nitrite inhibits macrophage tumoricidal
       activity and modulates inducible nitric oxide.
 DT    9504
 AU    Soderberg LS; Barnett JB; Department of Microbiology and Immunology,
       University of Arkansas; for Medical Sciences, Little Rock.
 SO    J Leukoc Biol. 1995 Jan;57(1):135-40. Unique Identifier : AIDSLINE
       MED/95131070
 AB    Abuse of nitrite inhalants is common among male homosexuals and a
       history of abuse has been correlated with seropositivity to HIV and with
       the incidence of Kaposi's sarcoma among AIDS patients. The present study
       shows that inhalation exposure of mice to 900 ppm isobutyl nitrite for
       45 min/day for 14 days compromised macrophage tumoricidal activity by up
       to 40% and it remained compromised for at least 7 days after terminating
       exposures. The inhalation exposures did not affect tumor cell binding
       but did inhibit inducible nitric oxide (NO zero). The NO zero synthase
       inhibitor NG-methyl-L-arginine totally inhibited both NO zero production
       and cytotoxicity, suggesting that reductions in NO zero due to inhalant
       exposure may be responsible for the reduced cytotoxic activity. Exposure
       to the inhalant increased constitutive production of tumor necrosis
       factor-alpha (TNF-alpha). TNF-alpha has been reported to stimulate the
       replication of HIV and the proliferation of Kaposi's sarcoma cells in
       vitro.
 DE    Administration, Inhalation  Animal  Arginine/ANALOGS &
       DERIVATIVES/PHARMACOLOGY  Cell Adhesion/DRUG EFFECTS  Cell Division/DRUG
       EFFECTS  Cell Transformation, Neoplastic/*DRUG EFFECTS/IMMUNOLOGY/
       PATHOLOGY  Cells, Cultured  Cytotoxicity, Immunologic/DRUG
       EFFECTS/IMMUNOLOGY  Dose-Response Relationship, Drug  Enzyme-Linked
       Immunosorbent Assay  Female  Interferon Type II/PHARMACOLOGY  Killer
       Cells, Natural/DRUG EFFECTS/IMMUNOLOGY/PATHOLOGY
       Lipopolysaccharides/PHARMACOLOGY  Macrophages, Peritoneal/*DRUG
       EFFECTS/IMMUNOLOGY/METABOLISM  Mice  Mice, Inbred C57BL  Nitric
       Oxide/ANTAGONISTS & INHIB/*METABOLISM/PHYSIOLOGY
       Nitrites/ADMINISTRATION & DOSAGE/*TOXICITY  Sarcoma,
       Kaposi's/ETIOLOGY/PATHOLOGY  Support, U.S. Gov't, P.H.S.  Tumor Necrosis
       Factor/METABOLISM/PHYSIOLOGY  Vasodilator Agents/ADMINISTRATION &
       DOSAGE/*TOXICITY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).