Estimation of Radiation-Induced Interphase Cell Death in Cultures of Human Tumor Material and in Cell Lines

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Abstract:

A short-term assay method able to estimate the radiation response of human cancer tissue samples would be of great advantage to the individualization of radiotherapy in cancer patients. However, the effect of radiation on [3H]thymidine incorporation by proliferating cells reflects a composite of cell cycle arrest and induced cell death pathways. Here we consider whether it is feasible to correct for cell cycle effects based on comparison of the effects of radiation and the mitotic inhibitor paclitaxel on [3H]thymidine incorporation. Sixty-two short-term (7-day) cultures of human tumor tissue from 61 patients with melanoma, gynecological cancer, brain cancer, and head and neck cancer, as well as 18 5-day cultures of low passage human tumor cell lines, were irradiated at doses from 2 to 9 Gy, or exposed to paclitaxel (200 nM). [3H]Thymidine incorporation was measured at the end of the incubation. Cell cycle times could be estimated from the paclitaxel data and were 2.7 to 18.6 days for melanomas, 2.5 to >40 days for carcinomas, 3.9 to 39 days for brain tumors, and 1.1 to 3.8 days for cell lines. The effects of radiation on [3H]thymidine incorporation varied widely (0–97% and 0–99% inhibition for 2 and 9 Gy, respectively), and in 23 of the clinical samples, but in none of the cell lines, radiation caused significantly greater inhibition of 3H]thymidine incorporation than paclitaxel (p < 0.05). We argue that that these differences reflect radiation-induced cell loss from G1 phase and/or S phase. Responses of short-term cultures of clinical tumor material to radiation, with appropriate correction for cell cycle effects, might have the potential to provide information on radiation-induced cell death in individual patients.

Keywords: Apoptosis; Human tumors; Interphase cell death; Paclitaxel; Radiosensitivity

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504003773994833

Affiliations: 1: *Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand 2: †Department of Clinical Oncology, Auckland Hospital, Auckland, New Zealand 3: ‡Department of Neurosurgery, Auckland Hospital, Auckland, New Zealand 4: §Department of Surgery, Auckland Hospital, Auckland, New Zealand 5: ¶Department of Histology, Green Lane Hospital, Auckland, New Zealand 6: #Department of Otolaryngology, Green Lane Hospital, Auckland, New Zealand 7: **Department of Urology, Auckland Hospital, Auckland, New Zealand 8: ††Palmerston North Hospital, Palmerston North, New Zealand 9: ‡‡Department of Obstetrics and Gynaecology, National Women’s Hospital, Auckland, New Zealand

Publication date: January 1, 2003

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

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