Rapid-mixing studies of the mechanisms of chemical radiosensitization and protection in mammalial cells

Abstract

A continuous flow, rapid-mixing system has been constructed to measure the degree of radiosensitization or protection observable after incubation of Chinese hamster ovary cells at room temperature for periods from about 5 to 1000 ms with a number of radiation modifiers. In agreement with Adams et al. (1975) full sensitization by oxygen is obtained in only a few tens of milliseconds. Misonidazole (10 mM) sensitizes at very nearly the steady-state level (E.R. approximately 2.3) in about 300 ms. Similarly near maximum sensitization by 10 mM metronidazole is seen within the same period. For large effects to be observed in such short times makes unlikely the involvement of any biochemical modification of either the drug or cells. Radioprotection by 1 M dimethyl suplhoxide reaches about 80% of the equilibrium control value within 850 ms. However, if its mode of action involves scavenging of hydroxyl radicals in competition with cellular components, the necessity for very high concentrations in the immediate region of the cellular target would be expected to require longer diffusion times. Cysteamine (10 mM) shows no evidence of its substantial protective ability even after 850 ms incubation. This molecule, which alone in this group exists as an ion in neutral solution, may encounter considerable difficulty in entering the cells.