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Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity.
- Source :
-
Chemical research in toxicology [Chem Res Toxicol] 2015 Dec 21; Vol. 28 (12), pp. 2250-2. Date of Electronic Publication: 2015 Nov 11. - Publication Year :
- 2015
-
Abstract
- This rapid report focuses on the pharmacodynamic mechanism of the carboplatin/paclitaxel combination and correlates it with its cytotoxicity. Consistent with the synergistic to additive antitumor activity (the combination index ranging from 0.53 to 0.94), cells exposed to this combination had significantly increased carboplatin-DNA adduct formation when compared to that of carboplatin alone (450 ± 30 versus 320 ± 120 adducts per 10(8) nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 10(8) nucleotides per hour in carboplatin alone (p = 0.021). This rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.
- Subjects :
- Antineoplastic Combined Chemotherapy Protocols pharmacology
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Antineoplastic Combined Chemotherapy Protocols toxicity
Carboplatin therapeutic use
Carboplatin toxicity
Cell Line, Tumor
Cell Survival drug effects
DNA Adducts therapeutic use
DNA Adducts toxicity
Drug Synergism
Humans
Paclitaxel therapeutic use
Urinary Bladder Neoplasms drug therapy
Carboplatin metabolism
DNA Adducts metabolism
Paclitaxel pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5010
- Volume :
- 28
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Chemical research in toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 26544157
- Full Text :
- https://doi.org/10.1021/acs.chemrestox.5b00422