Effect of a pure anti‐estrogen, ICI 182,780, on the in vitro radiosensitivity of MCF‐7 breast carcinoma cells

Abstract

AbstractUse of the anti‐estrogen tamoxifen (TAM) has been demonstrated to contribute a survival advantage in postmenopausal women with early stage or advanced breast cancer. Although conflicting results exist in the literature, some reports have suggested that TAM may exert potential deleterious effects on radiation sensitivity and response of breast cancers to radiotherapy (RT). A new non‐steroidal anti‐estrogen, ICI 182,780, which, unlike TAM, is without any estrogenic properties, has been used in European clinical trials in place of TAM. This study reports the effects of ICI 182,780 on radiation sensitivity and potentially lethal damage repair (PLDR) in estrogen‐receptor positive (ER+) MCF‐7 human breast carcinoma cells irradiated in vitro. At a concentration of 10−7 M, ICI 182,780 can inhibit the growth‐stimulatory effect of 10−10M 17β‐estradiol (E2). Growth‐arrested MCF‐7 cells were divided into four treatment groups: estradiol‐deprived (−E2) and estradiol‐stimulated (+E2) cultures incubated in the presence or absence of ICI 182,780 (10−7 M). Five days later each group was exposed to γ‐irradiation and cell survival was measured by clonogenic assay in complete medium containing E2. In one series of experiments, the cells were harvested immediately after irradiation, while in a second series, the cells were held at 37°C for an additional 24 hr prior to harvesting. No statistically significant survival difference was detected between groups plated immediately after irradiation or 24 hr later, although a trend toward improved survival for the delayed plating groups was routinely observed. ICI 182,780 did not significantly alter radiation sensitivity of MCF‐7 cells regardless of their hormonal status (+/−E2), nor did it change the sensitivity of cells harvested immediately or allowed 24 hr to express PLDR. These results suggest that ICI 182,780 may be used as an adjuvant in the treatment of breast cancer without altering the radiation sensitivity of breast cancer cells to concurrent RT. © 1995 Wiley‐Liss, Inc.