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Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity

Journal Article · · Chemical Research in Toxicology
 [1];  [1];  [1];  [1];  [2];  [2];  [1];  [3]
  1. Univ. of California, Davis, CA (United States). Dept. of Internal Medicine
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Univ. of California, Davis, CA (United States). Dept. of Internal Medicine; Univ. of California, Davis, CA (United States). Dept. of of Urology; VA Northern California Health Care System, Mather, CA (United States)
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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 108 nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 108 nucleotides per hour in carboplatin alone (p = 0.021). In conclusion, this rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.
Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1282117
Alternate ID(s):
OSTI ID: 1438658
Report Number(s):
LLNL-JRNL--737061
Journal Information:
Chemical Research in Toxicology, Journal Name: Chemical Research in Toxicology Journal Issue: 12 Vol. 28; ISSN 0893-228X
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English

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Cited By (5)

DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine journal December 2016
Effect of Gallic acid in potentiating chemotherapeutic effect of Paclitaxel in HeLa cervical cancer cells journal June 2019
Radiocarbon Tracers in Toxicology and Medicine: Recent Advances in Technology and Science journal May 2019
A novel and fully validated hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma journal March 2018
Combination Treatment with an Antibody–Drug Conjugate (A1mcMMAF) Targeting the Oncofetal Glycoprotein 5T4 and Carboplatin Improves Survival in a Xenograft Model of Ovarian Cancer journal July 2019

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