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Title: Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity

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). In conclusion, this rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.

Authors:
 [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)
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1282117
Alternate Identifier(s):
OSTI ID: 1438658
Report Number(s):
LLNL-JRNL-737061
Journal ID: ISSN 0893-228X
Grant/Contract Number:  
AC52-07NA27344; 1I01BX001784; CA 093373; GM103483-15
Resource Type:
Accepted Manuscript
Journal Name:
Chemical Research in Toxicology
Additional Journal Information:
Journal Volume: 28; Journal Issue: 12; Journal ID: ISSN 0893-228X
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Jiang, Shuai, Pan, Amy W., Lin, Tzu-yin, Zhang, Hongyong, Malfatti, Michael, Turteltaub, Kenneth, Henderson, Paul T., and Pan, Chong-xian. Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity. United States: N. p., 2015. Web. doi:10.1021/acs.chemrestox.5b00422.
Jiang, Shuai, Pan, Amy W., Lin, Tzu-yin, Zhang, Hongyong, Malfatti, Michael, Turteltaub, Kenneth, Henderson, Paul T., & Pan, Chong-xian. Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity. United States. doi:10.1021/acs.chemrestox.5b00422.
Jiang, Shuai, Pan, Amy W., Lin, Tzu-yin, Zhang, Hongyong, Malfatti, Michael, Turteltaub, Kenneth, Henderson, Paul T., and Pan, Chong-xian. Fri . "Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity". United States. doi:10.1021/acs.chemrestox.5b00422. https://www.osti.gov/servlets/purl/1282117.
@article{osti_1282117,
title = {Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity},
author = {Jiang, Shuai and Pan, Amy W. and Lin, Tzu-yin and Zhang, Hongyong and Malfatti, Michael and Turteltaub, Kenneth and Henderson, Paul T. and Pan, Chong-xian},
abstractNote = {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.},
doi = {10.1021/acs.chemrestox.5b00422},
journal = {Chemical Research in Toxicology},
number = 12,
volume = 28,
place = {United States},
year = {2015},
month = {11}
}

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