Activation And Deactivation Of Quinones Catalyzed By Dt-Diaphorase. Evidence For Bioreductive Activation Of Diaziquone (Azq) In Human Tumor Cells And Detoxification Of Benzene Metabolites In Bone Marrow Stroma
- 1 January 1990
- journal article
- research article
- Published by Taylor & Francis in Free Radical Research Communications
- Vol. 8 (4-6), 373-381
- https://doi.org/10.3109/10715769009053371
Abstract
Bioactivation of diaziquone (AZQ) in HT-29 human colon carcinoma cells and detoxification of benzene metabolites in bone marrow stromal cells were used as examples of the potential role of DT-diaphorase in both activation and deactivation processes. HT-29 cell cytosol contained high levels of DT-diaphorase activity and removed AZQ in the presence of either NADH or NADPH. Prior boiling of cytosol. omission of NADH or NADPH or inclusion of dicoumarol. an inhibitor of DT-diaphorase. inhibited removal of AZQ. AZQ-inouced cytotoxicity in HT-29 cells was also inhibited by dicoumarol. Chemical reduction of AZQ in a cell free system enhanced formation of a GSH conjugate of AZQ. Two of the major cell types in bone marrow stroma are macrophages and fibroblastoid stromal cells. A fibroblastoid cell line derived from stromal cells contained approximately fourfold higher levels of DT-diaphorase than macrophages. Inclusion of dicournarol in incubations containing 14C-hydroquinone and the respective stromal cell type, significantly increased covalent binding of radiolabel to macromolecules in stromal fibroblasts but not in macrophagesKeywords
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