Thymidine Sensitivity and Deoxynucleotide Pools of Human Lymphoid and Melanoma Cells in Vitro
Exposure of cells to excessive amounts of thymidine (dThd) may cause inhibition of DNA synthesis due to a depletion of deoxycytidine 5′-triphosphate (dCTP). Thymidine 5′-triphosphate (dTTP) accumulates in dThd-treated cells and leads to inhibition of ribonucleotide reductase-mediated synthesis of cytosine deoxynucleotides1. The toxic effects of dThd have been investigated with various mammalian cells in vitro. Notably, lymphoid cells of T-cell origin, but not of B-cell origin, are highly sensitive to dThd2,3. In vitro and in vivo studies have been reported demonstrating the therapeutic potential of high-dose dThd treatment against melanoma4–6. However, no deoxynucleotide metabolism studies on melanoma cells have been reported. In the present study we compared human T- and B- cells and melanoma cells in vitro with respect to dThd sensitivity, deoxynucleotide pool profiles and changes in deoxynucleotide levels in response to dThd.
KeywordsMelanoma Cell High Pressure Liquid Chromatography Nucleotide Pool NC37 Cell Pool Profile
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- 8.A. Leyva, H. Appel, and H.M. Pinedo, Purine modulation of thymidine activity in L1210 leukemia cells in vitro, Leukemia Res., in press.Google Scholar