Molecular effects of 2′,2′-difluorodeoxycytidine (gemcitabine) on DNA replication in intact HL-60 cells☆
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Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures compromise the cytostatic activity of the anticancer drug gemcitabine
2014, Journal of Biological ChemistryCitation Excerpt :Gemcitabine (2′,2′-difluoro-2′-deoxycytidine, dFdC; Fig. 1) is widely used in the treatment of various carcinomas, including pancreas, lung, breast, and bladder cancer (2). Phosphorylated dFdC metabolites act as inhibitors of ribonucleotide reductase and CTP synthetase, resulting in decreased intracellular dNTP (i.e. dCTP) levels, and the drug functions as a DNA chain terminator when incorporated as its 5′-triphosphate metabolite (dFdCTP) into the DNA (3, 4). First dFdC is phosphorylated to its 5′-monophosphate derivative (dFdCMP) by 2′-deoxycytidine kinase.
Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo
2017, Antiviral ResearchCitation Excerpt :HRV1B infection induced mild but distinct infiltration of inflammatory cells, mainly lymphoid cells and a few neutrophils, in the terminal air ways and alveoli, which was ameliorated by treatment with gemcitabine (Fig. 5D∼5F). Gemcitabine triphosphate (dFdCTP), the main metabolite of gemcitabine (dFdC) generated by deoxycytidine kinase, competes with dCTP for incorporation into DNA, and results in DNA damage (Heinemann et al., 1990; Ross and Cuddy, 1994). Gemcitabine inhibits DNA polymerase and other enzymes associated with deoxycytidine metabolism, including ribonucleotide reductase (Heinemann et al., 1990), deoxycytidylate deaminase (Heinemann et al., 1992), and CTP synthetase (Heinemann et al., 1995).
Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay
2016, Mutation Research - Genetic Toxicology and Environmental MutagenesisCitation Excerpt :Patients 07 and 26, both of whom had high PIG-A MFs, were treated with gemcitabine (GEM) and TS-1, respectively, in the absence of radiation therapies, suggesting that the higher PIG-A MFs were caused by chemotherapy but not by radiation therapy (Fig. 1 and Tables 1 and 2). GEM is a fluorinated deoxycytidine analogue that inhibits ribonucleotide reductase and can be incorporated into DNA, thus inhibiting DNA replication [21–23]. In mice, GEM treatment induced a significant increase in total chromosomal aberrations and the frequency of micronuclei in vivo [24].
Alteration of the carbohydrate for deoxyguanosine analogs markedly changes DNA replication fidelity, cell cycle progression and cytotoxicity
2010, Mutation Research - Fundamental and Molecular Mechanisms of MutagenesisHigh-performance liquid chromatographic method for the determination of gemcitabine and 2′,2′-difluorodeoxyuridine in plasma and tissue culture media
2006, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesRadiation modifiers: Treatment overview and future investigations
2006, Hematology/Oncology Clinics of North America
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Presented in part at the 83rd Annual Meeting of the American Association for Cancer Research, Orlando, FL, May 1993, and to the Workshop on Gemcitabine: Status of Pre-Clinical Studies, Free University Hospital, Amsterdam, The Netherlands, March 1994.