Differences in xenobiotic detoxifying activities between bone marrow stromal cells from mice and rats: Implications for benzene-induced hematotoxicity
- Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD (United States)
benzene is a human carcinogen; exposure can result in aplastic anemia and leukemia. Data from animal models are frequently used in benzene risk assessment. In rodent studies, mice are more sensitive to benzene-induced hematotoxicity than rats. Bone marrow stromal cells from mice were significantly more susceptible to the cytotoxicity induced by the benzene metabolites hydroquinone (HQ) and benzoquinone (BQ) than cells from rats. Since cellular gluthathione (GSH) and quinone reductase (QR) are known to play critical roles in modulating HQ-induced cytotoxicity, the GSH content and the QR and glutathione S-transferase (GST) activity in stromal cells from both species was measured. In rat cells, the GSH content and the QR specific activity were 2 and 28 times as much as those from mice, respectively. GSH and QR in both mouse and rat stromal cells were inducible by 1,2-dithiole-3-thione (D3T). D3T pretreatment of both mouse and rat stromal cells resulted in a marked protection against HQ-induced toxicity. Pretreatment of both mouse and rat stromal cells with GSH ethyl ester also provided a dramatic protection against HQ-induced toxicity. Conversely, dicoumarol, an inhibitor of QR, enhanced the HQ-induced toxicity in stromal cells from both mice and rats, indicating an important role for QR in modulating HQ-induced stromal toxicity. Buthionine sulfoximine (BSO), which depleted GSH significantly in both species, potentiated the HQ-induced toxicity in mouse but not in rat stromal cells. Surprisingly, incubation of stromal cells with BSO resulted in a significant induction of QR, especially in rats. Overall, this study demonstrates that the differences in stromal cellular GSH content and QR activity between mice and rats contribute to their respective susceptibility to HQ-induced cytotoxicity in vitro, and may be involved in the greater in vivo sensitivity of mice to benzene-induced hematotoxicity. 51 refs., 9 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 387346
- Journal Information:
- Journal of Toxicology and Environmental Health, Vol. 46, Issue 2; Other Information: PBD: Oct 1995
- Country of Publication:
- United States
- Language:
- English
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