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Roa WHY , Chapman JD
Killing of EMT-6 cells by decays from isotopes incorporated on sensitizer adducts
Radiation Research. 1992 ;132(2) :248-253
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EMT-6 tumor cell killing by decays from 3H and 125I incorporated by adduct formation of radiolabeled sensitizers was studied in vitro. Hypoxic radiosensitizers become covalently bound to cellular molecules after metabolic reduction, and EMT-6 tumor cells can tolerate over 109 adducts/cell of misonidazole without loss of colony-forming ability. Cells were incubated under hypoxic conditions in the presence of [3H]misonidazole or [125I]iodoazomycinriboside for various times and the amounts of bound 3H and 125I were determined. Cells were stored as monolayers at 22°C, in suspension culture at 4°C, and frozen in complete medium plus 8% DMSO at - 196°C for various times to facilitate the accumulation of radioactive decays before plating in vitro for colony-forming assays at 37°C. At 22°C in monolayer culture, EMT-6 tumor cells tolerated 950 and 1720 decays/cell of 3H and 125I, respectively, without evidence of radiotoxicity. This number of decays/cell over the exposure times used represents 1.54 x 1063H/cell and 8.4 x 104125I/cell, respectively. Significant cell killing was detected after similar amounts of isotope decay when cells were held at 4°C. When cells were frozen in the presence of 8% DMSO, they were more resistant to inactivation by isotope decays or by ? rays than cells in liquid phase at 4°C. These data suggest that selective hypoxic tumor cell suicide by 3H or 125I decays from bound sensitizer at 37°C will be an inefficient process, at least for drugs with specific activities as tested. These data are consistent with data on cell inactivation by isotopes incorporated into cells by other procedures.
00337587 (ISSN) Cited By: 0; Export Date: 31 May 2006; Source: Scopus CODEN: RAREA Language of Original Document: English Correspondence Address: Chapman, J.D.; Tumor Biology and Biophysics; Fox Chase Cancer Center; 7701 Burholme Avenue Philadelphia, PA 19111, United States Chemicals/CAS: dimethyl sulfoxide, 67-68-5; iodine 125, 14158-31-7, 22822-81-7; misonidazole, 13551-87-6; tritium, 10028-17-8, Cobalt Radioisotopes; Iodine Radioisotopes; iodoazomycin arabinoside, 138172-12-0; Misonidazole, 13551-87-6; Nitroimidazoles; Radiation-Sensitizing Agents; Tritium, 10028-17-8