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Molecular Pharmacology, Volume 52, Issue 5, 882-885

Epirubicin-Induced Oxidative DNA Damage and Evidence for Its Repair in Lymphocytes of Cancer Patients Who Are Undergoing Chemotherapy

Ryszard Olinski, Pawel Jaruga, Marek Foksinski, Karol Bialkowski, and Jerzy Tujakowski

Department of Clinical Biochemistry, University School of Medical Sciences, ul. Karlowicza 24, 85-092 Bydgoszcz, Poland (R.O., P.J., M.F., K.B.), and Provincial Center of Oncology, 85-793 Bydgoszcz, Poland (J.T.)

Anthracycline derivatives have been widely used in the treatment of several types of human malignancies. Cytotoxicity of these drugs has been attributed to inhibition of topoisomerase II as well as intracellular production of free radicals. In our work we used a gas chromatography/mass spectrometry technique to study free radical-induced DNA base modifications in chromatin isolated from lymphocytes of cancer patients who received chemotherapy with epirubicin (one of anthracycline's antitumor derivatives). The anticancer therapy caused significant increases in the amount of all four DNA base modifications over control levels in the lymphocytes of most of the patients. For the majority of the cases the base products returned to the control value 24 hr after the infusion of the drug, which suggests the removal of these lesions by cellular repair processes. However, some of the modified bases escaped repair. Because part of these modifications may possess premutagenic properties, they may be responsible for secondary cancers induced by chemotherapy.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics