Differential effects of buthionine sulphoximine in hypoxic and non-hypoxicregions of human cervical carcinoma xenografts

Background and Purpose: Recently we reported increased glutathione (GSH) le vels in hypoxic regions of ME 180 and SiHa cervical cancer xenografts. Sinc e this association might act synergistically to protect from radiotherapy, we examined the differential effects of the GSH depleting agent buthionine suiphoximine (BSO) in relation to tumor oxygenation. Materials and methods: The nitroimidazole EF5 was used to label tumor hypox ia. GSH levels were determined in cryostat sections using a sensitive HPLC assay and in parallel sections using fluorescence image analysis. Using a d ual-labeling method, GSH levels were determined selectively in hypoxic and non-hypoxic tumor regions. Results: GSH levels were higher in hypoxic than in non-hypoxic regions of c ervical carcinoma xenografts. Treatment with BSO produced a more pronounced GSH depletion in regions of hypoxia, resulting in similar post-treatment l evels in hypoxic and non-hypoxic areas. Conclusions: BSO effectively depletes GSH in hypoxic microregions of tumors . These findings suggest a potential role for BSO as an adjunct to radiothe rapy in cervical cancer patients. (C) 2001 Elsevier Science Ireland Ltd. Al l rights reserved.