Enhancement of X-ray Toxicity in Squamous Cell Carcinoma Cell Lines by DNA Polymerase Inhibitors

Abstract

The effect of the DNA polymerase inhibitors adenine 9-β-arabinofurasonide (ara-A), cytosine 1-β-arabinofuranoside (ara-C), and aphidicolin on X-radiation sensitivity was studied in a group of exponentially growing squamous cell carcinoma cell lines. The tumour cell lines varied in radiation sensitivity, with D₀ (radiation sensitivity) values ranging from 1·0 to 3·9 Gy. The addition of non-toxic concentrations of ara-A 30 min before irradiation and removal 30 min after irradiation potentiated cell killing in five of eight cell lines. Four of these five responsive cell lines were relatively radioresistant lines, having D₀ > 2·0 Gy. One of the cell lines was more radiosensitive (D₀ = 1·4 Gy). Ara-A was also effective in potentiating killing in the radioresistant cell lines even when added 60 min after irradiation. Pre- or post-treatment with ara-A had no effect on X-ray sensitivity of the other three relatively sensitive cell lines (D₀ ranging from 1·0 to 1·3 Gy). Both ara-C and aphidicolin were effective in potentiating X-ray sensitivity in JSQ-3, a relatively resistant cell line that was sensitized by ara-A treatment, but they had no effect on the X-ray sensitivity of SCC-61, a relatively radiosensitive cell line that was insensitive to ara-A effects on X-ray response. At the concentrations used, the polymerase inhibitors were equally effective in inhibiting DNA synthesis.