Residual proliferative capacity in F9 teratocarcinoma stem cell cultures treated with alpha-difluoromethylornithine, an inducer of parietal endoderm differentiation

Cancer Letters
M WallonO Heby

Abstract

We have previously shown that inhibition of polyamine biosynthesis by treatment with 5 mM alpha-difluoromethylornithine (DFMO) causes growth arrest and induces differentiation of F9 teratocarcinoma stem cells. The resulting phenotype is similar to that of parietal endoderm, and these differentiated cells possess no apparent proliferative capacity. In the present study, however, it is demonstrated that some of the DFMO-treated cells are not terminally differentiated. Upon a change to DFMO-free growth medium these cells eventually start to proliferate. Using a colony forming efficiency assay, it is estimated that less than 1 out of 200,000 cells retains its proliferative capacity after 6-10 days of DFMO treatment. These cells exhibit no apparent resistance to DFMO, and their population doubling time is similar to that of untreated control F9 cells. Consequently, the possible existence of a small, quiescent, cell population possessing proliferative potential must be taken into account when designing therapeutic protocols for DFMO.

References

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Citations

Aug 1, 1996·Cancer·J D Ahlgren
Jul 17, 1996·International Journal of Cancer. Journal International Du Cancer·M WatanabeM Asaka
Jan 3, 2001·Teratogenesis, Carcinogenesis, and Mutagenesis·F OzawaM W Büchler
Jul 1, 1995·Journal of Gastroenterology and Hepatology·J D CollierR Lendrum
Jul 4, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Jiyoung Kim, René Villadsen

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