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

Purpose: To compare the cytotoxicity of 125I-oestrogen (E-17alpha[125I]iodovinyl-11betamethoxyoestradiol or 125IVME2) 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 125IVME2 or [125I]iododeoxyuridine (125IdU), frozen for decay accumulation, thawed and then plated for colony formation. gamma-irradiation survival was also determined. A whole-cell 3H-oestrogen-binding assay and a specific-binding assay were used to detect ER.

Results: No MDA-231 cell killing by accumulated 125IVME2 decays (up to 440 dpc) was observed but ER-positive MCF-7 cells were killed by 125IVME2 (D(o)=28 dpc). MDA-231 cells were not significantly more radioresistant to gamma-rays (D(o)=1.7Gy for MDA-231 cells; 1 Gy for MCF-7 cells) or to 125IdU 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 125IVME2 decay accumulation. It is speculated that without ER (required to translocate the 125IVME2 to its nuclear target), formation of the 125IVME2-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.