An in vitro assessment of determinants of susceptibility of mouse bone marrow stromal cells to hydroquinone-induced toxicity.
Twerdok LE; Rembish SJ; Trush MA
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 1990 Jan; :1-7
Primary stromal cells from BDA/2-mice were characterized, and the reduction in their ability to support granulopoiesis after exposure to the benzene (71432) metabolite hydroquinone (123319) (HQ) was studied. Bone marrow cells were harvested from male BDA/2-mice and used to establish a primary adherent stromal cell culture. The cell population was stable at 60% macrophages as determined by esterase staining 7 and 14 days after isolation. Quinone-reductase (QR) activity of the stromal cells assayed over the same period was also stable at approximately 30 nanomoles/minute/milligram protein. The effect of HQ induced toxicity on stromal cell supported granulopoiesis was assayed by granulocyte/monocyte colony formation. A significant reduction was seen in the number of colonies formed when bone marrow cells were cultured in conditioned media from stromal cells exposed for 12 days to a subtoxic concentration of 15 micromolar (microM) HQ compared to cells cultured in conditioned media from unexposed stromal cells. When stromal cells were pretreated with 75microM 1,2-dithiole-3-thione (DTT) for 24 hours prior to HQ treatment, no reduction in colony formation was observed, indicating no loss of stromal cell supported granulopoiesis. The authors conclude that BDA/2-mice stromal cell cultures are stable with respect to population composition and QR activity over the 14 period studied, that HQ induces reduction of stromal cell supported granulopoiesis, and that DTT affords protection against this aspect of HQ toxicity.
NIOSH-Grant; Cancer; In-vitro-study; Cell-cultures; Cell-function; Cytotoxic-effects; Monocyclic-aromatic-hydrocarbons; Mammalian-cells
Environmental Health Sciences Johns Hopkins University 615 North Wolfe Street Baltimore, MD 21205
Final Grant Report
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland
Johns Hopkins University, Baltimore, Maryland