Modification of radiation dose-rate sparing effects in a human carcinoma of the cervix cell line by inhibitors of DNA repair.
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. Agent were added 2 h prior to irradiation and removed after 24 h exposure. Differential effects among the inhibitors were observed; aphidicolin 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 A and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in the sparing of tumour cells during protracted irradiation.
D016590:Aphidicolin; D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D003037:Cobalt Radioisotopes; D004260:DNA Repair / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D066298:In Vitro Techniques; D009675:Novobiocin / Q000494:pharmacology; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D014740:Vidarabine / Q000494:pharmacology
D001549:Benzamides; D003037:Cobalt Radioisotopes; D004224:Diterpenes; D009675:Novobiocin; D016590:Aphidicolin; D002110:Caffeine; C025160:3-aminobenzamide; D014740:Vidarabine; D006918:Hydroxyurea