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Oxygen Dependency of Tumor Cell Killing in Vitro by Light-Activated Photofrin II

J. D. Chapman, C. C. Stobbe, M. R. Arnfield, R. Santus, J. Lee and M. S. McPhee
Radiation Research
Vol. 126, No. 1 (Apr., 1991), pp. 73-79
DOI: 10.2307/3578173
Stable URL: http://www.jstor.org/stable/3578173
Page Count: 7
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Oxygen Dependency of Tumor Cell Killing in Vitro by Light-Activated Photofrin II
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Abstract

Asynchronous populations of mouse EMT-6 tumor cells were treated with Photofrin II and exposed to various doses of 630 nm light in slowly stirred suspensions which had been equilibrated with various concentrations of oxygen. Survival curves were generated with cells exposed to 20 μg/ml Photofrin II in tissue culture medium for 1 h, a procedure which made it possible to remove more than 50% of the drug by washing. It is expected that under these conditions the drug would be loosely bound to cell surface and plasma membranes and in the cellular cytosol. Survival curves were also generated with cells exposed to 5 μg/ml Photofrin II for 20-24 h, a procedure which resulted in >90% of the drug being tightly bound within cells, presumably to cellular lipids and membranes. Oxygen was obligatory for killing cells which had been exposed for both "short term" and "long term" to Photofrin II. After 30-40 min of pregassing cells with nitrogen gas which contained precise levels of oxygen, the concentration required to reduce rates of cell killing to 50% of maximum was approximately 0.5% O2 (gas phase) for short-term drug exposures and ≤0.05% O2 for long-term drug exposures. Even after pregassing times of 90-120 min prior to light administration, a Km of ≃0.1% O2 was observed for cells exposed to the drug for the longer time. When the same cells were exposed to 137 Cs γ rays in this irradiation chamber, no change in radiation sensitivity was observed after 30 min of pregassing cells with all oxygen concentrations studied. These data suggest that photosensitizing reactions are more efficient when Photofrin II partitions into cellular lipids at longer exposure times and that lower oxygen concentrations are required for photocytotoxicity when the drug is within or near these cellular lipid targets.

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