Studies with 1,2-dithiole-3-thione as a chemoprotector of hydroquinone-induced toxicity to DBA/2-derived bone marrow stromal cells

Stromal cells from DBA/2 mouse bone marrow have been shown to be susceptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also alters the compositition of stromal cell population by preferentially killing stromal macrophages compared to stromal fibroblasts. This cytotoxicity can be prevented by 1,2-dithiole-3-thione (DTT) as a result of the induction of quinone reductase (QR), a quinone-processing enzyme and glutathione. The inductive activities of DTT protected stromal cells against HQ-induced impairment of stromal cell ability to support myelopoiesis. In vivo feeding of DTT to DBA/2 mice increased QR activity within the bone marrow compartment and protected bone marrow stomal cells isolated from the DTT fed animals from ex vivo HQ challenge. Thus, the inducibility of cellular defense mechanisims and xenobiotic-processing enzymes by chemoprotective agents such as DTT may be a useful stategy for protecting against chemically induced bone marrow toxicities.