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.
Highlights
BCNU and CCNU were held in ethanol until immediately (
No cell kill was observed after i.c. or clamped and unclamped s.c. 9L tumors were treated with MISO or HPMC
No cell kill in clamped tumors treated with 2.5mM is consistent with the results of the in vitro 9L experiments (Siemann et al, 1984). In both i.c. (Figure 1) and unclamped s.c. (Figures 2 and 3) tumours, MISO combined with either BCNU or CCNU produced no additional cell kill
Summary
The origin of the 9L cell line (Schmidek et al, 1971; Wheeler et al, 1984), the methods for maintaining the cells in culture (Wheeler et al, 1984), the implantation procedures for i.c. The Macmillan Press Ltd., 1984 characteristics (Wheeler & Wallen, 1980) have been described previously. Treatment was initiated either 12 days after implantation (i.c. tumours) or when the tumours were 200-500mg (s.c. tumours). BCNU and CCNU were obtained from Dr R. Engle at the Drug Research and Development Branch, and MISO was obtained from Dr V. BCNU was dissolved in ethanol and diluted in sterile saline to the final concentrations for injection. CCNU was dissolved in ethanol and diluted to the final concentrations for injection in a 0.3% solution of hydroxypropyl-methylcellulose (HPMC) in saline. BCNU and CCNU were held in ethanol until immediately (
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
