title: Increased production of tumor necrosis factor-alpha by bone marrow leukocytes following benzene treatment of mice.
abstract: Hematopoiesis is regulated by cytokines released from bone marrow stromal cells and mature leukocytes. Recent studies have identified these cells as targets for benzene-induced hematotoxicity. In the present studies we analyzed the effects of benzene treatment of mice on the production of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) by bone marrow leukocytes. Bone marrow cells isolated from control or benzene-treated mice (660 mg/kg, once/day, 3 days) were purified on lymphocyte separation medium. Cells were then cultured in the presence of varying concentrations of lipopolysaccharide (0.1-10 micrograms/ml) for 0.5-48 hr. IL-1, IL-6, and TNF-alpha activity in culture supernatants was then quantified. We found a significant (p less than or equal to 0.02) increase in TNF-alpha production by bone marrow leukocytes from benzene-treated mice when compared to cells from control animals. Furthermore, this increase was dependent on the macrophage-specific growth factor, colony stimulating factor-1. Benzene treatment was also found to induce a small but significant (p less than or equal to 0.02) increase in the production of IL-1 by bone marrow leukocytes. This increase was rapid and transient, occurring in supernatants collected 2 hr after inoculation of bone marrow cells into culture. In contrast, benzene treatment had no effect on the production of IL-6 by bone marrow leukocytes. These results demonstrate that benzene treatment of mice stimulates mature bone marrow leukocytes to produce elevated levels of growth regulatory cytokines.
authors.affiliation: Joint Graduate Program in Toxicology, Rutgers University, Piscataway, New Jersey 08855-0789.
authors.forename: L
authors.initials: L
authors.lastname: MacEachern
authors.forename: D L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001554:Benzene