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). This rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Pan
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Tzu-yin
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Lawrence Livermore National Laboratory , P.O. Box 808, Livermore, California 94551-0808, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Malfatti
authors.affiliation: Lawrence Livermore National Laboratory , P.O. Box 808, Livermore, California 94551-0808, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Turteltaub
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Henderson
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.|Department of Urology, University of California Davis , 4501 X Street, Room 3016, Sacramento, California 95817, United States.|Hematology and Oncology, VA Northern California Health Care System , 10535 Hospital Way, Mather, California 95655, United States.
authors.forename: Chong-xian
authors.initials: CX
authors.lastname: Pan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D016190:Carboplatin / Q000378:metabolism* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018736:DNA Adducts / Q000378:metabolism* / Q000627:therapeutic use / Q000633:toxicity; D004357:Drug Synergism; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
chemical_list: D018736:DNA Adducts; C096276:carboplatin-DNA adduct; D016190:Carboplatin; D017239:Paclitaxel