The inhibition of cellular recovery in human tumour cells by inhibitors of topoisomerase.
A human bladder carcinoma cell line was irradiated at high and low dose rates and exposed to camptothecin and VP16, inhibitors of topoisomerase I and topoisomerase II respectively. Although camptothecin substantially modified the cytotoxic effects of high dose rate irradiation, abolished low dose rate sparing and inhibited the repair of sublethal and potentially lethal damage, VP16 had no effect on the survival curves even at highly cytotoxic doses. Thus, it is argued that there is a role for topoisomerase I but not topoisomerase II in the repair of DNA damage induced by ionising radiation.
Musk
S R
SR
Radiotherapy Research Unit, Institute of Cancer Research, Sutton, Surrey, UK.
Steel
G G
GG
D002166:Camptothecin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D004338:Drug Combinations; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D002166:Camptothecin