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• W1923971719 endingPage "1323" @default.
• W1923971719 startingPage "1317" @default.
• W1923971719 abstract "We previously demonstrated that murine bone marrow stromal cells express high levels of cytochrome P4501B1 (CYP1B1) that metabolizes 7,12-dimethylbenza[a]anthracene (DMBA), and that DMBA activates the Ah receptor (AhR) in these cells in vitro. More recently, we reported that CYP1B1 is required for DMBA-induced lymphoblastoma formation in vivo. In this study, we addressed the hypothesis that bone marrow stromal cell CYP1B1, and not AhR activation, is required for DMBA-induced pre-B-cell apoptosis. Although DMBA did not directly cause apoptosis in pre-B cells, dose-dependent apoptosis of pre-B cells was observed when they were cocultured with a bone marrow stromal cell line. The DMBA 3,4-dihydrodiol metabolite was more potent in effecting pre-B-cell apoptosis than DMBA, whereas the potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin was inactive. Both pre-B cells and bone marrow stromal cells contained DMBA-diol-epoxide DNA adducts, indicating that reactive metabolites were transferred from stromal cells to pre-B cells. DMBA caused apoptosis when cocultured with primary bone marrow stromal cells isolated from AhR-null mice but not CYP1B1-null mice. When cocultured with AhR-null primary bone marrow stromal cells, DMBA induced approximately 50% of the pre-B-cell apoptosis seen with stromal cells from AhR-heterozygous mice. This reduced level of apoptosis parallels the decreased CYP1B1 expression in AhR-null mouse bone marrow stromal cells. These findings provide convincing evidence that bone marrow stromal cell CYP1B1 metabolism of DMBA, but not AhR activation, is required for DMBA-induced pre-B-cell apoptosis." @default.
• W1923971719 created "2016-06-24" @default.
• W1923971719 creator A5003497148 @default.
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• W1923971719 date "1999-12-01" @default.
• W1923971719 modified "2023-09-23" @default.
• W1923971719 title "Bone Marrow Stromal Cell Cytochrome P4501B1 Is Required for Pre-B Cell Apoptosis Induced by 7,12-Dimethylbenz[a]anthracene" @default.
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• W1923971719 doi "https://doi.org/10.1124/mol.56.6.1317" @default.
• W1923971719 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10570060" @default.
• W1923971719 hasPublicationYear "1999" @default.
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