Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin.

Blood
James H DoroshowEwa Gajewski

Abstract

In prior studies, it was demonstrated that the redox metabolism of doxorubicin leads to the formation of promutagenic oxidized DNA bases in human chromatin, suggesting a potential mechanism for doxorubicin-related second malignancies. To determine whether a similar type of DNA damage is produced in the clinic, peripheral blood mononuclear cell DNA from 15 women treated with infusional doxorubicin (165 mg/m(2)) as a single agent was examined for 14 modified bases by gas chromatography/mass spectrometry with selected ion monitoring. Prior to the 96-hour doxorubicin infusion, 13 different oxidized bases were present in all DNA samples examined. Chemotherapy, producing a steady-state level of 0.1 microM doxorubicin, increased DNA base oxidation up to 4-fold compared to baseline values for 9 of the 13 bases studied. Maximal base oxidation was observed 72 to 96 hours after doxorubicin treatment was begun; the greatest significant increases were found for Thy Gly (4.2-fold), 5-OH-Hyd (2.5-fold), FapyAde (2.4-fold), and 5-OH-MeUra (2.4-fold). The level of the promutagenic base FapyGua increased 1.6-fold (P < .02), whereas no change in 8-OH-Gua levels was observed in peripheral blood mononuclear cell DNA during the doxorubicin infusion....Continue Reading

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Citations

Aug 21, 2012·Antioxidants & Redox Signaling·V Ashutosh Rao
Feb 16, 2006·Journal of the National Cancer Institute·James H Doroshow
May 22, 2013·Expert Opinion on Pharmacotherapy·Ciara FreemanFrancis Giles
Mar 28, 2008·Expert Opinion on Drug Metabolism & Toxicology·Maria C Shoshan, Stig Linder
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Jun 26, 2012·Expert Opinion on Investigational Drugs·Jonathan A Abbas, Robert K Stuart
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Dec 24, 2013·Biochimica Et Biophysica Acta·Fan YangSteven Henikoff
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Aug 21, 2013·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Patrícia S GuerreiroNuno G Oliveira
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May 30, 2009·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Dora Il'yasovaRichard DiGiulio
Sep 14, 2019·Journal of Cellular Physiology·Ali Bashiri DezfouliJalal Hassan
Dec 31, 2019·Oxidative Medicine and Cellular Longevity·James H Doroshow
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May 1, 2021·Materials·Kamila ButowskaJacek Piosik
May 6, 2021·Journal of Food Biochemistry·Fayez ShaldoumEman M Abd-Ella

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