Lack of significant modulation of the formation and removal of platinum-DNA adducts by aphidicolin glycinate in two logarithmically-growing ovarian tumour cell lines in vitro.
Two recently established human ovarian carcinoma cell lines (JA-T and TR175) have been used to study the effects of aphidicolin glycinate (APG), a specific competitive inhibitor of DNA polymerase alpha (Ikegani et al. (1978) Nature, 275, 458-460), on the formation and removal of four platinum-DNA adducts. Logarithmically-growing cells were exposed to cis-diamminedichloroplatinum (II) (cisplatin) (10 micrograms, 33.4 microM) in the presence or absence of APG (5 or 50 micrograms/ml, 11.6 or 116 microM). Platinum-DNA adducts were quantitated using a competitive ELISA technique. No differences were observed between the initial levels of total DNA platination and of specific DNA adducts formed in the presence or absence of APG in either cell line. Following 18 h posttreatment incubation both lines showed some ability to remove each of the three main platinum-DNA lesions (Pt-GMP, Pt-AG and Pt-GG). However, the levels of these specific DNA adducts decreased over this time period, by similar rates with or without APG addition. It was also shown that the APG concentrations used had minimal inhibitory effects alone on growth or DNA synthesis during this 18 h posttreatment incubation period. Furthermore its addition did not significantly modify cisplatin-induced cytotoxicity, as judged by inhibition of growth or DNA synthesis over this time period. We therefore conclude that under these experimental conditions APG does not modulate 'repair' of cisplatin-induced DNA damage in logarithmically-growing cultures of these two apparently 'repair-proficient' human ovarian tumour cell lines.
Dempke
W C
WC
Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund, London, UK.
Shellard
S A
SA
Fichtinger-Schepman
A M
AM
Hill
B T
BT
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016590:Aphidicolin / Q000031:analogs & derivatives; D002945:Cisplatin / Q000378:metabolism / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004260:DNA Repair / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D006147:Guanine / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010984:Platinum / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D004224:Diterpenes; D016590:Aphidicolin; D010984:Platinum; D006147:Guanine; D004247:DNA; C068151:aphidicolin glycinate; D004257:DNA Polymerase II; D002945:Cisplatin