Ls. Yasui et al., Cytotoxicity of I-125-oestrogen decay in non-oestrogen receptor-expressinghuman breast cancer cells, MDA-231 and oestrogen receptor-expressing MCF-7cells, INT J RAD B, 77(9), 2001, pp. 955-962
Purpose: To compare the cytotoxicity of I-125-oestrogen (E-17 alpha[I-125]i
odovinyl-11 beta methoxyoestradiol or (125)IVME2) decay accumulation in hum
an breast adenocarcinoma cells that do not express oestrogen receptor (ER)
(MDA-231 cells) with human breast adenocarcinoma cells that do express ER (
Materials and methods: MDA-231 cells were labelled with (125)IVME2 or [I-12
5]iododeoxyuridine ((125)IdU), frozen for decay accumulation, thawed and th
en plated for colony formation. gamma -irradiation survival was also determ
ined. A whole-cell H-3-oestrogen-binding assay and a specific-binding assay
were used to detect ER.
Results: No MDA-231 cell killing by accumulated (125)IVME2 decays (up to 44
0 dpc) was observed but ER-positive MCF-7 cells were killed by (125)IVME2 (
D-o = 28 dpc). MDA-231 cells were not significantly more radioresistant to
gamma -rays (D-o =1.7 Gy for MDA-231 cells 1 Gy for MCF-7 cells) or to (125
)IdU decays (D-o = 44 dpc for MDA-231 cells: 30 dpc For MCF-7 cells). No ER
were detected in MDA-231 cells.
Conclusions: ER-negative cells, MDA-231, are not killed by (125)IVME2 decay
accumulation. It is speculated that without ER (required to translocate th
e (125)IVME2 to its nuclear target), formation of the (125)IVME2 ER DNA oes
trogen response element (ERE) complex and subsequent specific irradiation o
f the DNA at the ERE cannot occur. These results support the hypothesis tha
t the nuclear genome is a critical target for radiation-induced cell death.