Studies with 1,2-dithiole-3-thione as a chemoprotector of hydroquinone-induced toxicity to DBA/2-derived bone marrow stromal cells.
Twerdok-LE; Rembish-SJ; Trush-MA
Environ Health Perspect 1993 Jun; 101(2):172-177
The effects of 1,2-dithiole-3-thione (534258) (DTT) on hydroquinone bone marrow toxicity were investigated. Bone marrow stromal cells obtained from DBA/2-mice were preincubated with 0 or 75 micromolar (microM) DTT for 24 hours, then incubated with 0, 15, 35, or 50microM hydroquinone for 24 hours. Cytotoxicity was assessed by determining survival using the crystal-violet dye assay and effects on the ability of the cells to support myelopoiesis in granulocyte/monocyte cultures. Male DBA/2-mice were fed diets containing 0.1% DTT for 6 days, then killed, the femurs removed and bone marrow isolated. The bone marrow stromal cells were assayed for quinone-reductase (QR). The stromal cells were incubated with 50microM hydroquinone and the effects on survival determined. Hydroquinone at 35 and 50microM decreased stromal cell survival by 28 and 47%, respectively. DTT protected against hydroquinone induced cell killing. Hydroquinone at 15microM did not affect survival but significantly impaired the ability of the cells to support myelopoiesis. DTT abolished hydroquinone myelotoxicity. In- vivo, DTT feeding significantly increased bone marrow stromal cell QR activity. DTT partially protected against the decrease in survival induced by hydroquinone. The authors conclude that DTT protects mouse bone marrow stromal cells against hydroquinone toxicity by inducing QR activity. Induction of cellular defense mechanisms and xenobiotic metabolizing enzymes by chemoprotective agents such as DTT nay be a useful technique for protecting against chemical induced bone marrow toxicity.
NIOSH-Publication; NIOSH-Grant; Cancer; Quinones; Bone-marrow; In-vivo-studies; Laboratory-animals; In-vitro-studies; Cytotoxic-effects; Prophylaxis; Enzyme-activity
Environmental Health Sciences Johns Hopkins University 615 North Wolfe Street Baltimore, MD 21205
Environmental Health Perspectives
Johns Hopkins University, Baltimore, Maryland