Free radical scavengers can modulate the DNA-damaging action of alloxan.

• Authors: Janusz Blasiak , Agnieszka Sikora , Agnieszka Czechowska , Józef Drzewoski
• Languages of publication: EN

Abstracts

EN

Alloxan can generate diabetes in experimental animals and its action can be associated with the production of free radicals. It is therefore important to check how different substances often referred to as free radical scavengers may interact with alloxan, especially that some of these substance may show both pro- and antioxidant activities. Using the alkaline comet assay we showed that alloxan at concentrations 0.01-50 μM induced DNA damage in normal human lymphocytes in a dose-dependent manner. Treated cells were able to recover within a 120-min incubation. Vitamins C and E at 10 and 50 μM diminished the extent of DNA damage induced by 50 μM alloxan. Pre-treatment of the lymphocytes with a nitrone spin trap, α-(4-pyridil-1-oxide)- N-t-butylnitrone (POBN) or ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), which mimics glutathione peroxides, reduced the alloxan-evoked DNA damage. The cells exposed to alloxan and treated with formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (AlkA), enzymes recognizing oxidized and alkylated bases, respectively, displayed greater extent of DNA damage than those not treated with these enzymes. The results confirmed that free radicals are involved in the formation of DNA lesions induced by alloxan. The results also suggest that alloxan can generate oxidized DNA bases with a preference for purines and contribute to their alkylation.

Keywords

EN

vitamin C; spin trapping; free radicals; alloxan; vitamin E; DNA damage; ebselen; comet assay; DNA repair; diabetes mellitus

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2003
• Volume: 50
• Issue: 1
• Pages: 205-210

Dates

published

2003

received

2002-10-09

revised

2003-01-22

accepted

2003-02-19

Contributors

author

Janusz Blasiak

• Department of Molecular Genetics, University of Lodz, Łódź, Poland

author

Agnieszka Sikora

• Department of Molecular Genetics, University of Lodz, Łódź, Poland

author

Agnieszka Czechowska

• Department of Molecular Genetics, University of Lodz, Łódź, Poland

author

Józef Drzewoski

• Department of Clinical Pharmacology, Medical University of Lodz, Łódź, Poland

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