PURPOSE: To investigate changes in nucleotide metabolism after irradiation. MATERIALS AND METHODS: HT29 and SW48 human colon carcinoma cells were exposed to 60Co gamma-rays at doses ranging from 0 to 7.5 Gy. At different times after irradiation, the activities of nine enzymes involved in nucleotide metabolism were measured, the levels of thymidine kinase and deoxycytidine kinase proteins were evaluated by Western blot, and cell-cycle kinetics were analysed by flow cytometry. RESULTS: Changes in enzyme activities concerned not purine but pyrimidine metabolism and essentially the salvage pathway for deoxyribonucleotide synthesis. They were greater in the less radiosensitive HT29 cells. The levels of thymidine kinase and deoxycytidine kinase proteins changed in parallel with their activities. The metabolic changes in irradiated cells did not seem to be due to S-phase transition and the pattern of enzyme activity changes was different from that observed in proliferative cells. CONCLUSIONS: Radiation-induced changes in the salvage pathway for pyrimidine deoxyribonucleotide synthesis were observed. These findings could be exploited in cancer therapy because higher enzyme activities after irradiation suggest that radiation exposure may render cells more sensitive to the drugs activated by these enzymes.
PURPOSE: To investigate changes in nucleotide metabolism after irradiation. MATERIALS AND METHODS: HT29 and SW48 humancolon carcinoma cells were exposed to 60Co gamma-rays at doses ranging from 0 to 7.5 Gy. At different times after irradiation, the activities of nine enzymes involved in nucleotide metabolism were measured, the levels of thymidine kinase and deoxycytidine kinase proteins were evaluated by Western blot, and cell-cycle kinetics were analysed by flow cytometry. RESULTS: Changes in enzyme activities concerned not purine but pyrimidine metabolism and essentially the salvage pathway for deoxyribonucleotide synthesis. They were greater in the less radiosensitive HT29 cells. The levels of thymidine kinase and deoxycytidine kinase proteins changed in parallel with their activities. The metabolic changes in irradiated cells did not seem to be due to S-phase transition and the pattern of enzyme activity changes was different from that observed in proliferative cells. CONCLUSIONS: Radiation-induced changes in the salvage pathway for pyrimidine deoxyribonucleotide synthesis were observed. These findings could be exploited in cancer therapy because higher enzyme activities after irradiation suggest that radiation exposure may render cells more sensitive to the drugs activated by these enzymes.
Authors: Charles P Hinzman; Meth Jayatilake; Sunil Bansal; Brian L Fish; Yaoxiang Li; Yubo Zhang; Shivani Bansal; Michael Girgis; Anton Iliuk; Xiao Xu; Jose A Fernandez; John H Griffin; Elizabeth A Ballew; Keith Unger; Marjan Boerma; Meetha Medhora; Amrita K Cheema Journal: J Transl Med Date: 2022-05-10 Impact factor: 8.440
Authors: Carla F M Molthoff; Bianca M Klabbers; Johannes Berkhof; Jasper T Felten; Marcelle van Gelder; Albert D Windhorst; Ben J Slotman; Adriaan A Lammertsma Journal: Mol Imaging Biol Date: 2007 Nov-Dec Impact factor: 3.488
Authors: Katherine A McAllister; Akeel A Yasseen; George McKerr; C S Downes; Valerie J McKelvey-Martin Journal: Front Genet Date: 2014-08-08 Impact factor: 4.599
Authors: Yuri L Bunimovich; Evan Nair-Gill; Mireille Riedinger; Melissa N McCracken; Donghui Cheng; Jami McLaughlin; Caius G Radu; Owen N Witte Journal: PLoS One Date: 2014-08-07 Impact factor: 3.240