ABSTRACT
Intracerebral (i.c.) and subcutaneous (s.c.) 9L tumours were treated simultaneously with various doses of the nitrosoureas, BCNU or CCNU, and 2.5 mmol kg-1 of misonidazole (MISO). After 24 h, tumours were removed, dissociated into single cell suspensions and the cells plated for colony formation. In both i.c. and s.c. tumours, no cell kill was observed after exposure to MISO alone, and no additional cell kill was observed when MISO was combined with either nitrosourea. If s.c. 9L tumours were clamped 30 min after i.p. injection of 2.5 mmol kg-1 MISO, then 2 h later the clamps were removed and the nitrosourea injected, an increase in cell kill was observed. This increase in cell kill was statistically significant (P less than 0.01) for each dose of BCNU administered, but not statistically significant (P greater than 0.05) for the moderate dose of CCNU administered. Clamping did not alter the colony forming efficiency of cells from untreated 9L s.c. tumours or from those treated with each drug alone. These data demonstrate that hypoxic cells are required for misonidazole to potentiate the cell-killing effects of the nitrosoureas and that s.c. 9L tumours contain no such cells.
Subject(s)
Brain Neoplasms/drug therapy , Carmustine/therapeutic use , Lomustine/therapeutic use , Misonidazole/therapeutic use , Nitroimidazoles/therapeutic use , Oxygen/metabolism , Skin Neoplasms/drug therapy , Animals , Brain Neoplasms/pathology , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Synergism , Rats , Skin Neoplasms/pathology , Tumor Stem Cell AssayABSTRACT
Despite the fact that group counseling is emphasized in most drug treatment programs, client resistance to participation in groups is a common problem. Attitudinal differences between inner-city drug treatment clients and a graduate student sample were investigated as a possible factor contributing to resistance. Drug treatment clients were found to have less experience with counseling and therapy, and less understanding of the nature and purpose of the process.