Polyfunctional Radiosensitizers: V. Sensitization of Hypoxic Chinese Hamster Cells, V.79-753B, in Vitro by a Series of Bifunctional Nitroxyl Compounds

Abstract

MILLAR, B. C., JENKINS, T. C., AND FIELDEN, E. M. Polyfunctional Radiosensitizers. V. Sensitization of Hypoxic Chinese Hamster Cells, V.79-753B, in Vitro by a Series of Bifunctional Nitroxyl Compounds. Radiat. Res. 90, 271-283 (1982). A homologous series of uncharged nitroxyl biradicals have been examined as hypoxic cell sensitizers. In the series piperidinic nitroxyl moieties were separated by alkane-dicarboxamide bridging groups containing an increasing number (0 -o 7) of methylene groups. In each instance sensitization was characterized by changes in both extrapolation number (n) and the slope of the hypoxic cell survival curve. Increasing the cell-drug contact time from 1 to 3 hr produced an increase in the slope of the survival curve. This was not always associated with a further decrease in n. The present data support the hypothesis that lack of interaction between the radical centers in these and other bifunctional nitroxyls is important for events leading to shoulder modification. The degree of interaction between the radical moieties was assessed from their ESR spectra in solution. In addition, comparison has been made between charged and uncharged forms of a bifunctional nitroxyl compound. In this instance a 3-hr cell-drug contact time in the presence of the uncharged compound resulted in an increase in both slope and n, whereas there was no change in n when cells were irradiated in the presence of the charged compound. When cells which had been preexposed for 3 hr to a biradical, RSU-4072, were irradiated in the presence of a mixture of the biradical and the monoradical TMPN, the survival parameters were characteristic of those seen for TMPN alone. The implications of these results are discussed.