Effect of BSO on the radiation response at low (0-4 Gy) doses.
Depletion of thiols by various agents has been shown to radiosensitize hypoxic cells. The agent BSO is used to specifically inhibit GSH synthesis, and the effect of this treatment on radiation response, particularly in the region of clinical interest, was studied using automated microscopic identification of cells for measurement of high survival levels. In both CHO and V79 cell lines, the enhancement rations were greater at low doses (80% S) than at high doses (2% S) in cells irradiated in hypoxia. GSH depletion also affected the aerobic response in both dose regions, with again higher ER's observed at low doses. These results support previous studies which suggest that GSH levels affect the shoulder portion of the survival curve. However, as with untreated cells, the OER's remain higher at high doses than at low doses, in BSO treated cells of both lines. These studies complement an earlier low-dose study on diamide by Skarsgard and co-workers, and were carried out to increase our understanding of the factors which affect radiation sensitivity in the range of doses used in fractionated regimens in the clinic.
Skov
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KA
Medical Biophysics Unit, B.C. Cancer Research Centre, Vancouver, Canada.
MacPhail
H S
HS
D000818:Animals; D019328:Buthionine Sulfoximine; D016466:CHO Cells; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006224:Cricetinae; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase