PMID: 3755717Jul 1, 1986Paper

Oxygen and nitroreductase-dependent binding of AF-2 in spheroids and murine tumors

International Journal of Radiation Oncology, Biology, Physics
P L Olive, D J Chaplin

Abstract

Fluorescent nitroheterocycles such as AF-2 may be useful in identifying hypoxic cells in tumors. Since binding is dependent on rate of drug metabolism (nitroreduction) as well as cellular oxygen content, flow cytometric analysis of cells from tumors and spheroids was used to quantify AF-2 binding, and differential pulse polarography was used to measure reduction of AF-2 by several mammalian cell lines, spheroids and tumor cells. Hypoxic V79 spheroid cells and Lewis lung tumor cells bound 20 times more AF-2 than oxic cells, and binding proceeded with first order kinetics. Nitroreductase activity varied about tenfold among different tumor cells. As expected, the rate of binding of AF-2 correlated well with the rate of nitroreduction. Oral injection of AF-2 (5 mg) was the most successful method of administration to tumor-bearing mice. In mice injected with both AF-2 and Hoechst 33342 (which stains well-perfused cells), SCCVII tumor cells which contained the most Hoechst contained the least AF-2. Although minimal toxicity by AF-2 was observed in these tumors, binding of AF-2 was barely sufficient for detection using flow cytometry.

References

Nov 1, 1985·International Journal of Radiation Oncology, Biology, Physics·P L Olive
Aug 1, 1986·International Journal of Radiation Oncology, Biology, Physics·R E Durand, P L Olive
Aug 1, 1984·International Journal of Radiation Oncology, Biology, Physics·P L Olive
Aug 1, 1984·International Journal of Radiation Oncology, Biology, Physics·P WardmanM R Stratford

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Citations

Jan 1, 1987·Cancer Metastasis Reviews·J E Moulder, S Rockwell
Jan 1, 1992·International Journal of Radiation Oncology, Biology, Physics·P L OliveM J Trotter
Jun 1, 1989·International Journal of Radiation Oncology, Biology, Physics·P L Olive
Oct 26, 2010·Computer Methods and Programs in Biomedicine·Thomas R B GrandjeanTanya Coleman
Jun 22, 2010·Biotechnology and Bioengineering·Goutami BanerjeeJonathan D Walton
Mar 14, 2013·The Biochemical Journal·Jiechuang SuWilliam R Wilson

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