Radiosensitization of Mammalian Cells byp-nitroacetophenone

Abstract
The effectiveness of p-nitroacetophenone (PNAP) as a sensitizing agent to x-rays has been measured in asynchronous and synchronous populations of Chinese hamster cells. PNAP was found to sensitize hypoxic cells selectively (those equilibrated with an environment of 96 per cent N2 + 4 per cent CO2 containing less than 2 p.p.m. O2) with a maximum dose-modifying factor (DMF) of ∼ 1·50 at concentrations of 400 µM and greater in complete medium. In a parallel radiation scheme, the DMF for cells saturated with air was consistently between 2·75 and 3·05. In synchronously-growing Chinese hamster cells, the cyclic variation in surviving fraction measured for cells in air experiencing a radiation dose of 1055 rads could be reproduced for cells irradiated in hypoxic conditions with 2840 rads. We conclude that O2 sensitizes Chinese hamster cells in a dose-modifying fashion, irrespective of position in the cell-cycle. Hypoxic synchronized cells irradiated in the presence of PNAP with 1980 rads are also sensitized in all phases of the cell-cycle, PNAP being slightly more effective for S-phase cells. This differential sensitization is expressed by a two-fold reduction of the cyclic variation in cell sensitivity compared with that of cells irradiated in air or N2. The sensitizing ability of 500 µM PNAP was also determined for air-saturated and hypoxic mouse L-cells, and a selective hypoxic sensitization of ∼ 40 per cent of that of oxygen was measured.