Modification of Radiation Dose-rate Sparing Effects in a Human Carcinoma of the Cervix Cell Line by Inhibitors of DNA Repair

Abstract
The in vitro cell survival of a human cervix carcinoma cell line (HX156c) has been assessed using 60Co .gamma.-rays administered at either high (150 cGy/min) or low (3.2 cGy/min) dose rate. Recovery during low dose-rate irradiation was observed; the dose reduction factor at 10-2 cell kill for 150 versus 3.2 cGy/min was around 1:3. An insight into the possible underlying mechanisms of this recovery process has been investigated by addition of non-toxic concentrations of various agents thought to inhibit eukaryotic DNA repair. Agents were added 2 h prior to irradiation and removed after 24 h exposure. Differential efects among the inhibitors was observed; amphidicolin had no effect on cell survival, novobiocin, hydroxyurea and 3-aminobenzamide reduced survival by a similar extent at both dose rates, .beta.-ara A and caffeine reduced survival to a greater extent during low dose-rate irradiation. .beta.-ara A and caffeine seemed to exert their effects mainly by increasing the alpha component of the acute survival curve. Since survival curves obtained at dose rates of around 3 cGy/min help define a dominant component of the initial slope of the acute curve we have demonstrated that .beta.-ara and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in the sparing of tumour cells during protracted irradiation.

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