Enhanced radioresponse of paclitaxel-sensitive and -resistant turnouts in vivo

C. G. Milross, K. A. Mason, N. R. Hunter, N. H.A. Terry, N. Patel, S. Harada, T. Jibu, J. Seong, L. Milas

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Abstract

Paclitaxel is a potent chemotherapeutic drug and also has the potential to act as a radioenhancing agent. The latter is based on its ability to arrest cells in the radiosensitive G2M phases of the cell cycle; the weight of supporting evidence is derived mainly from in vitro studies. Our previous in vivo experiments identified enhanced tumour radioresponse predominantly attributable to turnout reoxygenation occurring as a result of paclitaxel- induced apoptosis. The current study investigated whether paclitaxel enhanced the radioresponse of turnouts which are insensitive to apoptosis induction, but exhibited mitotic arrest, and compared the degree and kinetics of the response to that in turnouts which develop apoptosis. The mouse mammary carcinoma MCA-29 (apoptosis sensitive) and the squamous cell carcinoma SGC- VII (apoptosis resistant) were used. In addition, the study investigated whether paclitaxel affected normal skin radioresponse to determine if a therapeutic gain could be achieved. Paclitaxel enhanced the radioresponse of both types of tumours. In the SCG-VII tumour, radiopotentiation occurred within 12 h of paclitaxel administration coincident with mitotic arrest, where enhancement factors (EFs) ranged from 1.15 to 1.37. In MCA-29 tumour, the effect was greater, EFs ranging from 1.59 to 1.91 and occurred between 24 and 72 h after paclitaxel when apoptosis was the predominant microscopic feature of treated tumours and when tumour oxygenation was found to be increased. The acute skin radioresponse and late leg contracture response were essentially unaffected by prior treatment with paclitaxel. Therefore, by two distinct mechanisms, paclitaxel was able to enhance the radioresponse of paclitaxel-sensitive and -resistant turnouts, but not the normal tissue radioresponse, thus providing true therapeutic gain.

Original languageEnglish
Pages (from-to)1299-1308
Number of pages10
JournalEuropean Journal of Cancer Part A
Volume33
Issue number8
DOIs
Publication statusPublished - 1997 Jul 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Milross, C. G., Mason, K. A., Hunter, N. R., Terry, N. H. A., Patel, N., Harada, S., Jibu, T., Seong, J., & Milas, L. (1997). Enhanced radioresponse of paclitaxel-sensitive and -resistant turnouts in vivo. European Journal of Cancer Part A, 33(8), 1299-1308. https://doi.org/10.1016/S0959-8049(97)00107-X