JaLCDOI 10.18926/AMO/31723
FullText URL fulltext.pdf
Author Araki, Shinako| Miyagi, Yasunari| Kawanishi, Kunihiro| Yamamoto, Junko| Hongo, Atsushi| Kodama, Junichi| Yoshinouchi, Mitsuo| Kudo, Takafumi|
Abstract <p>The in vitro radiosensitizing effects of docetaxel have been reported, but the DNA damage caused by the irradiation after docetaxel exposure has not been investigated. In this study, the authors attempted to evaluate the radiosensitizing effects in terms of cell survival and DNA single-strand breaks in a human ovarian adenocarcinoma cell line (known as line BG-1) and a human cervical squamous cell carcinoma cell line (known as line SiHa). The cell lines were exposed to various concentrations of docetaxel (from 2.27 x 10(-3) to 2.27 microg/ml) to investigate the cytocidal effects by colony-formation assay. DNA single-strand breaks after exposure to 2.27 microg/ml of docetaxel for 30 min or 100 min were measured by the alkaline-elution assay. The remarkable cytotoxicity of docetaxel followed by irradiation was observed when concentrations were greater than 2.27 x 10(-2) microg/ml in both cell lines. The combination of docetaxel and irradiation appears to be supraadditive. The DNA single-strand breaks induced by the irradiation were enhanced in both cell lines (BG-1; P &#60; 0.01, SiHa; P &#60; 0.05). The synergistic cytocidal effect cannot be explained quantitatively only by the single-strand breaks. </p>
Keywords docetaxel DNA single-strand break radiosensitizer
Amo Type Article
Published Date 2002-02
Publication Title Acta Medica Okayama
Volume volume56
Issue issue1
Publisher Okayama University Medical School
Start Page 13
End Page 18
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 11873939
Web of Sience KeyUT 000174031300003
JaLCDOI 10.18926/AMO/31635
FullText URL fulltext.pdf
Author Yamamoto, Junko| Miyagi, Yasunari| Kawanishi, Kunihiro| Yamada, Shinako| Miyagi, Yuji| Kodama, Junichi| Yoshinouchi, Mitsuo| Kudo, Takafumi|
Abstract <p>The pharmacodynamic effects of cisdiamminedichloroplatinum(II) (CDDP) in vitro have been reported, but the dosage and exposure time in vitro have not been based on clinical observations of the drug's actions in vivo. In this study, the authors attempted to evaluate the pharmacodynamic effects of CDDP in vitro in terms of cell survival and DNA crosslinking by simulating unbound CDDP administration at varying concentrations to a rat mammary adenocarcinoma line (known as line 66). CDDP exposure was conducted by both constant concentration procedures and a simulated in vivo procedure. Colony formation assay for the surviving fraction and alkaline elution assay for DNA crosslink measurement were performed in order to evaluate the pharmacodynamics of CDDP. Cell survival was a function of the area under the drug concentration time curve (AUC) of unbound CDDP (R2 = 0.77, P &#60; 0.002) for all drug exposure procedures as analyzed by the analysis of covariance test. There was a strong correlation between the surviving fraction and the crosslink index of the total amount of DNA crosslinks (R2 = 0.85, P &#60; 0.0005). Both the total amount of DNA-DNA crosslinks and the DNA-protein crosslinks, of which the latter were dominant, were affected not by the exposure procedures, but by the AUC value (P &#60; 0.002). The thresholds of cytocidal effect were 1.59 mg.h/l for the AUC and 0.008 for the crosslink index. The pharmacodynamic effects in vitro by simulated in vivo exposure were identical to those of constant.</p>
Keywords pharmacodynamics pharmacokinetics simulation cisplatin crosslink
Amo Type Article
Published Date 1999-10
Publication Title Acta Medica Okayama
Volume volume53
Issue issue5
Publisher Okayama University Medical School
Start Page 201
End Page 208
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 10561728
Web of Sience KeyUT 000083427100001