| Literature DB >> 27657672 |
Tiffany M Scharadin1, Hongyong Zhang1, Maike Zimmermann1,2, Sisi Wang1, Michael A Malfatti3, George D Cimino2, Kenneth Turteltaub3, Ralph de Vere White4, Chong-Xian Pan1,2, Paul T Henderson1,2.
Abstract
Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. We determined whether subtherapeutic "microdoses" of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of 14C-labeled gemcitabine for 4-24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. These results support gemcitabine levels in DNA as a potential biomarker of drug cytotoxicity.Entities:
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Year: 2016 PMID： 27657672 PMCID： PMC5385140 DOI： 10.1021/acs.chemrestox.6b00247
Source DB: PubMed Journal: Chem Res Toxicol ISSN： 0893-228X Impact factor: 3.739