[125I]iodotamoxifen cytotoxicity in cultured human (MCF-7) breast cancer cells.

Abstract

We evaluated the uptake and radiotoxicity of [125I]iodotamoxifen (125ITAM) in MCF-7 human breast cancer cells in the presence or absence of excess non-radioactive estradiol (E2) or iodotamoxifen (ITAM). Studies in cells under wash-out conditions and in nuclei isolated from previously exposed cells showed that 125ITAM binds estrogen receptor (ER) and antiestrogen binding sites (AEBS) and has the capacity for considerable non-specific binding. The radiotoxicity of 125ITAM was a complex function related to ER content and/or function as well as interactions with ER, AEBS and non-specific binding. Addition of E2 or ITAM abolished ER mediated cell killing. ITAM but not E2 abolished AEBS mediated cytotoxicity. Non-specific binding accounted for considerable cytotoxicity. Although these studies confirm the radiotoxicity of nuclear bound 125I, multiple nuclear binding sites, variability in ER content and function and non-specific binding will all adversely influence ultimate clinical efficacy.

• Authors: W H McLaughlin, K M Pillai, J P Edasery, R D Blumenthal, W D Bloomer
• Journal: Journal of steroid biochemistry (J Steroid Biochem) Vol. 33 Issue 4A Pg. 515-9 (Oct 1989) ISSN: 0022-4731 [Print] England
• PMID: 2811361 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Iodine Radioisotopes
• Receptors, Estrogen
• Tamoxifen
• iodotamoxifen

Topics

• Breast Neoplasms (metabolism, radiotherapy)
• Humans
• Iodine Radioisotopes (administration & dosage)
• Receptors, Estrogen (metabolism)
• Tamoxifen (pharmacokinetics)
• Tumor Cells, Cultured (metabolism, radiation effects)