The role of subcellular localization in assessing the cytotoxicity of iodine-125 labeled iododeoxyuridine, iodotamoxifen, and iodoantipyrine

Autor: W. H. McLaughlin, D.E. Seitz, Ralph R. Weichselbaum, Stephen Adelstein, William D. Bloomer, Robert N. Hanson
Rok vydání: 1981
Předmět:
Zdroj: Journal of Radioanalytical Chemistry. 65:209-221
ISSN: 1588-2780
0134-0719
DOI: 10.1007/bf02516105
Popis: There is abundant evidence that Auger effects from125I are singularly damaging if localized within DNA as the thymidine analogue125I-iododeoxyuridine (125IUdR). Recent work with125I-labeled intercalating agents and steroid sex hormones extends these observations by showing cytotoxicity with125I in sites other than the DNA backbone. We have compared the cytotoxicity of125IUdR,125I-iodotamoxifen, a non-steroidal antiestrogen that is translocated from the cytoplasm to the nucleus of receptor containing cells, and125I-iodoantipyrine, a biological indicator of the body water space, in human breast cancer cells (MCF-7) and report that cytotoxicity is critically dependent upon subcellular localization. When clonogenic survival of MCF-7 cells is expressed as a function of the concentration of125IUdR,125ITAM and125IAP in the culture media, the D37 values are 8·10−4, 2.3 and 68 μCi/ml, respectively. However, when survival is expressed as a function of the nucleic acid and protein subcellular fraction,125ITAM is just about as toxic as125IUdR localized within the DNA backbone.
Databáze: OpenAIRE