Cytotoxicity of 125 I-oestrogen decay in non-oestrogen receptor-expressing human breast cancer cells, MDA-231 and oestrogen receptor-expressing MCF-7 cells

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Abstract
Purpose : To compare the cytotoxicity of 125 I-oestrogen (E-17 α [ 125 I]iodovinyl-11 β methoxyoestradiol or 125 IVME2) decay accumulation in human breast adenocarcinoma cells that do not express oestrogen receptor (ER) (MDA-231 cells) with human breast adenocarcinoma cells that do express ER (MCF-7 cells). Materials and methods : MDA-231 cells were labelled with 125 IVME2 or [ 125 I]iododeoxyuridine (125 IdU), frozen for decay accumulation, thawed and then plated for colony formation. γ-irradiation survival was also determined. A whole-cell 3 H-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 440 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 γ-rays (D o =1.7Gy for MDA-231 cells; 1 Gy for MCF-7 cells) or to 125 IdU decays (D o = 44dpc 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 the 125 IVME2 to its nuclear target), formation of the 125 IVME2-ER-DNA oestrogen-response element (ERE) complex and subsequent specific irradiation of the DNA at the ERE cannot occur. These results support the hypothesis that the nuclear genome is a critical target for radiation-induced cell death.

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