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 composition of stromal cell populations 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 cytotoxicity and 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 stromal cells isolated from the DTT-fed animals from ex vivo HQ challenge. Thus, the inducibility of cellular defense mechanisms and xenobiotic-processing enzymes by chemoprotective agents such as DTT may be a useful strategy for protecting against chemically induced bone marrow toxicities.
Twerdok
L E
LE
Department of Enviornmental Health Sciences, Division of Toxicological Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Rembish
S J
SJ
Trush
M A
MA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D004305:Dose-Response Relationship, Drug; D006873:Hydroquinones / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology; D013871:Thiones / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D006873:Hydroquinones; D013871:Thiones; D013876:Thiophenes; D016660:NAD(P)H Dehydrogenase (Quinone); C049325:1,2-dithiol-3-thione; C031927:hydroquinone