Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells
| Autor: | Hettinga, JVE, Lemstra, W, Meijer, C, Dam, WA, Uges, DRA, Konings, AWT, DeVries, EGE, Kampinga, HH |
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| Přispěvatelé: | University of Groningen, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
inorganic chemicals
DNA-ADDUCTS REPAIR HEAT THERMAL ENHANCEMENT female genital diseases and pregnancy complications CYTO-TOXICITY cisplatin-DNA adducts MAMMALIAN-CELLS HUMAN FIBROBLASTS CIS-DIAMMINEDICHLOROPLATINUM(II) cisplatin accumulation cisplatin resistance DRUG neoplasms thermochemosensitization adduct repair ACQUIRED-RESISTANCE |
| Zdroj: | British Jounal of Cancer, 75(12), 1735-1743. Nature Publishing Group |
| ISSN: | 0007-0920 |
| Popis: | In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 43 degrees C during cDDP exposure was found to increase drug accumulation significantly in the cDDP-resisiant cell lines but had little effect on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation, however, was significantly increased in all cell lines studied. Furthermore, ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment was enhanced and/or adduct removal was decreased in heated cells, resulting in relatively more DNA damage remaining at 24 h after the end of cDDP exposure. Correlation plots with survival revealed weak correlations with cellular Pi accumulation (r(2) = 0.59) and initial Pt-DNA adduct formation (r(2) = 0.64). Strong correlations, however, were found with Pt-DNA adducts at 6 h (r(2) = 0.97) and 24 h (r(2) = 0.89) after the incubation with the drug. In conclusion, the mechanism by which heat sensitizes cells for cDDP action seems to be the sum of multiple factors, which comprise heat effects on accumulation, adduct formation and adduct processing. This mechanism did not seem to differ between cDDP-sensitive and -resistant cells, emphasizing the potential of hyperthemia to reduce cDDP resistance. |
| Databáze: | OpenAIRE |
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