Finding
It is suggested that although uptake of the drug is rapid, probably occurring by passive diffusion, an additional mechanism not involving gross metabolism and operating on the time scale of seconds to minutes is required to produce maximal sensitization
Paper
A rapid-mixing comparison of the mechanisms of radiosensitization by oxygen and misonidazole in CHO cells.
Abstract
The mechanisms of hypoxic cell radiosensitization by oxygen and by the 2-nitroimidazole chemical sensitizer, misonidazole, were studied in CHO cells using rapid-mixing techniques. Both agents display a dose response of sensitivity in steady-state experiments which is satisfactorily fitted by a K function with maximum enhancement ratios (ER) of about 2.8. Rapidmixing experiments demonstrated that oxygen sensitization in these cells is complete within about 10 msec even at concentrations as low as 2.6% oxygen, with no evidence for two timeresolved components as had been reported with V79 cells [Shenoy, M. A., Asquith, J. C., Adams, G. E., Michael B. D., and Watts, M. E. Radiat. Res. 62, 498-512 (1975)]. Full sensitivity persists for at least 165 msec following an 8.4-fold dilution into hypoxic medium. No large temperature dependence was observed in the range 4 to 370C. Partial development of sensitization by misonidazole also occurs very quickly, within 25 msec with a 10 mM drug concentration, but only to an ER of about 1.7, much below the level observed after many minutes incubation ('2.5) even at ice temperature. This development, too, has a very weak temperature dependence. It is suggested that although uptake of the drug is rapid, probably occurring by passive diffusion, an additional mechanism not involving gross metabolism and operating on the time scale of seconds to minutes is required to produce maximal sensitization
Authors
D. Whillans, J. Hunt
Journal
Radiation research