Radiosensitization of Mammalian Cells by p-Nitroacetophenone

Summary

Analogues of p-nitroacetophenone (PNAP) have been tested on Chinese-hamster cells for their ability to inhibit cell proliferation (measure of toxicity) and to sensitize hypoxic cells to x-rays. Compounds with different substituents at the para position on the benzene ring showed capabilities of interfering with cell proliferation which could be correlated with their electronegativities. Using the 50 per cent ‘inhibition of proliferation’ value as an estimate of toxicity, the analogues showed decreasing toxicity in the order p-NO₂ > p-Cl, p-Br > p-OCH₂ > p-CH₃ > p-NH₂ > acetophenone. Of these compounds only PNAP sensitized hypoxic mammalian cells to x-rays in the concentration ranges tested.

Studies with isomers of PNAP showed that m-nitroacetophenone was less toxic, as well as less effective as a sensitizer, than either o-nitroacetophenone or or PNAP. Mechanisms of toxicity and radiosensitization are discussed in relation to the electron affinities of the compounds.