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Damage of Trypanosoma cruzi deoxyribonucleic acid by nitroheterocyclic drugs
Authors:S G Goijman  A C Frasch  A O Stoppani
Affiliation:1. The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK;1. Key Lab of Education Ministry for Power Machinery and Engineering, School of Mechanical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China;2. School of Material Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China;3. Gas Turbine Research Institute, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
Abstract:Kinetoplast DNA (kDNA) from Trypanosoma cruzi epimastigotes pretreated with the trypanocidal drugs nifurtimox (10 or 100 microM) or benznidazole (38 or 380 microM) showed an increased number of strand-breaks, as revealed by (a) trapping of alkali-denatured kDNA by nitrocellulose filters and (b) electrophoresis in an alkaline 2% agarose gel. Similar damage was observed in nuclear DNA (nDNA), as detected by centrifugation in an alkaline-sucrose gradient. DNA damage was reversible since reincubation in fresh medium for 24 hr restored filtration and electrophoretic and sedimentation patterns to normal.
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