title: Estimation of radiation-induced interphase cell death in cultures of human tumor material and in cell lines.
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.
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Marshall
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: John H L
authors.initials: JH
authors.lastname: Matthews
authors.forename: Chakiath C
authors.initials: CC
authors.lastname: Jose
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Furneaux
authors.forename: James H F
authors.initials: JH
authors.lastname: Shaw
authors.forename: James A
authors.initials: JA
authors.lastname: Kirker
authors.forename: Randall P
authors.initials: RP
authors.lastname: Morton
authors.forename: Julian B
authors.initials: JB
authors.lastname: White
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rice
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Isaacs
authors.forename: Richard
authors.initials: R
authors.lastname: Coutts
authors.forename: John R
authors.initials: JR
authors.lastname: Whittaker
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007399:Interphase / Q000187:drug effects / Q000528:radiation effects*; D009369:Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D017239:Paclitaxel