scholarly journals Synergistic cytotoxicity and DNA strand breaks in cells and plasmid DNA exposed to uranyl acetate and ultraviolet radiation

2014 ◽  
Vol 35 (4) ◽  
pp. 338-349 ◽  
Author(s):  
Janice Wilson ◽  
Mary C. Zuniga ◽  
Filbert Yazzie ◽  
Diane M. Stearns
Keyword(s):  
Ultraviolet Radiation ◽  
Plasmid Dna ◽  
Dna Strand Breaks ◽  
Uranyl Acetate ◽  
Strand Breaks ◽  
Synergistic Cytotoxicity ◽  
Dna Strand ◽  
In Cells

Formation of plasmid DNA strand breaks induced by low-energy ion beam: indication of nuclear stopping effects

1998 ◽  
Vol 37 (2) ◽  
pp. 101-106 ◽  
Author(s):  
Y. Chen ◽  
Bingyao Jiang ◽  
Youshan Chen ◽  
Xingzhao Ding ◽  
Xianghuai Liu ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Ion Beam ◽  
Dna Strand Breaks ◽  
Low Energy ◽  
Strand Breaks ◽  
Nuclear Stopping ◽  
Dna Strand

Assessment of evidence for nanosized titanium dioxide-generated DNA strand breaks and oxidatively damaged DNA in cells and animal models

2017 ◽  
Vol 11 (9-10) ◽  
pp. 1237-1256 ◽  
Author(s):  
Peter Møller ◽  
Ditte Marie Jensen ◽  
Regitze Sølling Wils ◽  
Maria Helena Guerra Andersen ◽  
Pernille Høgh Danielsen ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Animal Models ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Nanosized Titanium Dioxide ◽  
Dna Strand ◽  
Assessment Of Evidence ◽  
In Cells ◽  
Damaged Dna

scholarly journals Bioreduction of Idarubicin and Formation of ROS Responsible for DNA Cleavage by NADPH-Cytochrome P450 Reductase and its Potential Role in the Antitumor Effect

2009 ◽  
Vol 11 (4) ◽  
pp. 68 ◽  
Author(s):  
Haydar Çelik ◽  
Emel Arinç
Keyword(s):  
Dna Damage ◽  
Cytochrome P450 ◽  
Plasmid Dna ◽  
Antitumor Effect ◽  
Dna Strand Breaks ◽  
Cytochrome P450 Reductase ◽  
Strand Breaks ◽  
P450 Reductase ◽  
Nadph Cytochrome P450 Reductase ◽  
Dna Strand

PURPOSE. Idarubicin is a clinically effective synthetic anthracycline analog used in the treatment of several human neoplasms. Anthracyclines have the potential to undergo bioactivation by flavoenzymes to free radicals and thus exert their cytotoxic actions. In this study, our main objective was to investigate the possible involvement of NADPH-cytochrome P450 reductase in the bioreductive activation of idarubicin to DNA-damaging species. METHODS. A pBR322 plasmid DNA damage assay was used as a sensitive method for detecting strand breaks in DNA exposed to idarubicin in the presence of P450 reductase and cofactor NADPH under various incubation conditions. In addition, the rates of idarubicin reduction by P450 reductases purified from phenobarbital-treated rabbit liver, beef liver and sheep lung microsomes were determined by measuring NADPH oxidation at 340 nm. RESULTS. The plasmid DNA experiments demonstrated that idarubicin could undergo bioreduction by P450 reductase with the resulting formation of DNA strand breaks. The antioxidant enzymes SOD and catalase, and hydroxyl radical scavengers, DMSO and thiourea, afforded significant levels of protection against idarubicin-induced DNA strand breaks. These findings suggested that DNA damage by idarubicin occurs through a mechanism which involves its redox cycling with P450 reductase to generate reactive oxygen species (ROS). The extent of DNA damage by idarubicin was found to increase with increasing concentrations of drug or enzyme as well as with increasing incubation time. The capacity of idarubicin to induce DNA damage under above incubation conditions was compared with that of a model compound, mitomycin C. Finally, enzyme assays carried out with purified P450 reductases revealed that idarubicin exhibited about two-fold higher rate of reduction than mitomycin C. CONCLUSION. Our findings implicated bioreduction of idarubicin by P450 reductase and subsequent redox cycling under aerobic conditions as being one mode of idarubicin action potentially contributing to its antitumor effect.

Sign in / Sign up

Export Citation Format

Share Document