Studies on biochemical determinants of quinone-induced toxicity in primary murine bone marrow stromal cells.
Twerdok LE; Trush MA
Adv Exp Med Biol, Biological Reactive Intermediates IV: Molecular and Cellular Effect and Their Impact on Human Health, Proceedings of the Fourth International Symposium on Biological Reactive Intermediates, January 14-17, 1990, Tucson, Arizona. Witmer CM, ed., NY: Plenum Press, 1991 Feb; 283:843-846
Susceptibility to quinone (106514) generating metabolites of benzene (71432) and quinone-reductase (QR) activity in cultured bone marrow stromal cells derived from male DBA/2-mice was investigated. In order to identify underlying mechanisms of 1,2-dithiole-3-thione (DTT) chemoprotection, the effect of DTT on QR and glutathione-S- transferase (GST) activities in the stromal cells was assessed. DTT induced QR activity in primary stroma cells in a dose dependent manner. There were no corresponding changes in GST activity, indicating that induction of QR activity may be important in DTT's chemoprotection. Basal QR activity and percent esterase remained essentially constant in the beginning 2 to 3 weeks of primary culture of bone marrow stroma. The macrophages appeared to be more sensitive to HQ induced toxicity than the fibroblastic element of bone marrow stroma as indicated by treatment with HQ which increased QR activity, but reduced the percent esterase positive cells. DTT pretreatment 24 hours prior to administering HQ restored the percent esterase positive cells to control levels. In-vivo feeding studies with DTT induced QR activity within the bone marrow compartment. The authors conclude that QR activity and its inducibility may be important factors in chemically induced bone marrow toxicity and carcinogenicity.
NIOSH-Publication; NIOSH-Grant; Cancer; Metabolic-study; Enzyme-activity; Carcinogens; Carcinogenesis; Bone-marrow; Toxic-effects; Laboratory-animals; In-vitro-studies
Environmental Health Sciences Johns Hopkins University 615 North Wolfe Street Baltimore, MD 21205
Advances in Experimental Medicine and Biology. Biological Reactive Intermediates IV: Molecular and Cellular Effect and Their Impact on Human Health, Proceedings of the Fourth International Symposium on Biological Reactive Intermediates, January 14-17, 1990, Tucson, Arizona
Johns Hopkins University, Baltimore, Maryland