Cell-line specific radiosensitizing effect of zalcitabine (DDC)

The potential of zalcitabine (ddC) to act as an ionizing radiation response modifier was tested on exponentially growing human cancer
cells in vitro. Two human cell lines, WiDr (colon) and MCF-7 (breast) were exposed to ddC at 10 p M concentration for various lengths
of tide (18, 24, 48 and 72 h). On the WiDr cell line the dual effect of concentration and duration of exposure prior to irradiation was
investigated. Experimental endpoints were clonogenicity and viability, as measured by colony formation assay (CFA) and MTT assay
respectively. The impact on cell-cycle distribution prior to irradiation was assessed by flow cytometry using a double labeling technique
(propidium iodide and bromodeoxyuridine pulse label). A significant reduction in surviving fraction and viability was observed for
WiDr-cells irradiated after pre-exposure to 10 pM for 18, 48 and 72 h as compared to corresponding irradiated controls. At lower
concentrations (1 and 5 pM), the radiosensitizing effect was only significant after a 72-h exposure (assessed by CFA). For MCF-7, ddC
induced a significant modification of the dose response only with 24 and 48 h preincubation. However, the overall effect was less
pronounced as compared to WiDr. Cell-cycle analysis showed accumulation in S-phase, 48 and 72 h after treatment with 10 pM ddC in
the WiDr cells, with a progressive shift to late S-phase as shown by the biparametric analysis. The degree of radiosensitization is cell-line
dependent with the most important sensitization observed on the most <<radioresistant cell line>>, ix., the cell line with the lowest alpha
value and highest SF 2 (WiDr). For WiDr, radiosensitization by ddC depends on the duration of exposure and the concentration of the
drug.
Received 29 February 1996
Accepted 10 December 1996