NDLI: Depletion of tumour versus normal tissue glutathione by buthionine sulfoximine.

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Depletion of tumour versus normal tissue glutathione by buthionine sulfoximine.

Content Provider	CiteSeerX
Author	Lee, F. Y. F. Allalunis-Turner, M. J. Siemann, D. W.
Abstract	Summary We have investigated in detail the effects of buthionine sulfoximine (BSO), a selective glutathione (GSH) depleting agent, on the GSH contents of a number of normal tissues and three experimental tumours in mice. Significant variations in the rate and degree of GSH depletion and recovery were observed among the normal tissues. Following a dose of 2.5 mmol kg-1 BSO, GSH nadirs were reached by approximately 5 h for the liver and kidney, 8 h for the lung and bone marrow, 12 h for red blood cells (RBCs) and by 24 h for the heart. The degree of depletion was greatest for the kidney (80%), liver (74%) and bone marrow (83%), intermediate for the heart (54%) and lung (40%), and least for RBCs (13%). Recovery of GSH content was fastest for the liver followed in descending order by the kidney, the lung, the bone marrow, RBCs and the heart. In contrast, the rate and extent of GSH depletion and recovery showed considerably less variation among the 3 murine tumours. In the tumours GSH nadirs were reached by 10-12h. The extent of depletion was about 55-65%. Recovery of GSH levels in the tumours required 48 h or more, a longer period than required by the liver, kidney and lung but shorter than that needed for the bone marrow, heart and RBCs. Attempts to preferentially deplete tumour GSH by exploiting the differences in recovery rates between normal tissues and tumours were only partially successful. Multiple BSO dosing at 16 h intervals allowed the liver to recover between doses, but the recovery in the kidney, lung and bone marrow was only partial and no
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Subject Keyword	Buthionine Sulfoximine Tumour Versus Normal Tissue Glutathione Normal Tissue Gsh Content Gsh Depletion Mmol Kg-1 Bso Gsh Nadir Red Blood Cell Gsh Level Selective Glutathione Tumour Gsh Recovery Rate Experimental Tumour Multiple Bso Dosing Murine Tumour Tumour Gsh Nadir Significant Variation
Content Type	Text

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