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 susce ptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also alters th e composition of stromal cell populations by preferentially killing st romal macrophages compared to stromal fibroblasts. This cytotoxicity c an be prevented by 1,2-dithiole-3-thione (DTT) as a result of the indu ction of quinone reductase (QR), a quinone-processing enzyme, and glut athione. The inductive activities of DTT protected stromal cells again st HQ-induced cytotoxicity and against HQ-induced impairment of stroma l cell ability to support myelopoiesis. In vivo feeding of DTT to DBA/ 2 mice increased QR activity within the bone marrow compartment and pr otected bone marrow stromal cells isolated from the DTT-fed animals fr om ex vivo HQ challenge. Thus, the inducibility of cellular defense me chanisms and xenobiotic-processing enzymes by chemoprotective agents s uch as DTT may be a useful strategy for protecting against chemically induced bone marrow toxicities.