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Lookup NU author(s): Suzanne Kyle,
Professor barbara Durkacz
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We have investigated the effects of the protein kinase inhibitor wortmannin (WM) on the cytotoxic mechanisms of etoposide and ionising radiation (IR) in the Chinese hamster ovary K1 (CHO-K1) cell line, and its radiation-sensitive derivative, xrs-6, which is defective in DNA-dependent protein kinase (DNA-PK) function. WM potentiated the cytotoxicity of etoposide and IR in CHO-K1 cells approximately 1.6 and 3-fold, respectively, and this potentiation was abolished in xrs-6 cells, which were themselves more sensitive to etoposide and IR alone. WM partially inhibited the repair of etoposide-induced DNA double-strand breaks. Etoposide treatment caused a biphasic inhibition of DNA synthesis in both cell lines, and this was abrogated by co-incubation with WM. These data suggest that WM inhibits in intact cells both DNA-PK and either or both the ataxia telangiectasia (AT) and AT-related gene products ATM and ATR. (C) 2000 Elsevier Science Ltd.
Author(s): Boulton, S., Kyle, S., Durkacz, B.W.
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Print publication date: 01/03/2000
ISSN (print): 0959-8049
ISSN (electronic): 1359-6349
PubMed id: 10717533
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