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

• Autorzy: Blasiak J. , Sikora A. , Czechowska A. , Drzewoski J.
• Języki publikacji: EN

Abstrakty

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 uM 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 uM diminished the extent of DNA damage induced by 50 uM alloxan. Pre-treatment of the lymphocytes with a nitrone spin trap, a-(4-pyridil-1-oxide)- .-t-butylnitrone (POBN) or ebselen (2-phenyl-1,2-benzisoselenazol-3(2.H)-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 alkyl- ated 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.

Słowa kluczowe

EN

vitamin C; vitamin E; DNA repair; diabetes mellitus; DNA damage; spin trapping; free radical; alloxan

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2003
• Tom: 50
• Numer: 1
• Opis fizyczny: p.205-210,fig.

Twórcy

autor

Blasiak J.

• University of Lodz, S.Banacha 12-16, 90-237 Lodz, Poland

autor

Sikora A.

autor

Czechowska A.

autor

Drzewoski J.

Bibliografia

• Blasiak J, Kowalik J. (2000) Mutat Res.; 469: 135-45.
• Bromme HJ, Morke W, Peschke D, Ebelt H, Peschke D. (2000) J Pineal Res.; 29: 201-8. Collins AR, Duthie SJ, Dobson VL. (1993) Carcinogenesis.; 14: 1733-5.
• Donnini D, Zambito AM, Perrella G, Ambesi-Impiombato FS, Curicio F. (1996) Biochem Biophys Res Commun.; 219: 412-7.
• Evans MD, Podmore ID, Daly GJ, Perrett D, Lunec J, Herbert KE. (1997) Biochem J; 325: 1-16. Gasparutto D, Dherin C, Boiteux S, Cadet J. (2002) DNA Repair.; 1: 437-47. Klaude M, Eriksson S, Nygren J, Ahnstrom G. (1996) Mutat Res.; 363: 89-96. Lenzen S, Munday R. (1991) Biochem Pharmacol.; 42: 1385-91. Murata M, Imada M, Inoue S, Kawanishi, S. (1998) Free Radic Biol Med.; 25: 586-95. Sakurai K, Ogiso T. (1991) Chem Pharm Bull.; 39: 737-42.
• Sies H. (1991) Oxidative stress: from basic research to clinical application, pp 619 Academic Press, San Diego.
• Singh NP, McCoy MT, Tice RR, Schneider EL. (1988) Exp Cell Res.; 175: 184-91.
• Szkudelski T, Kandulska K, Okulicz M. (1998) Physiol Res.; 47: 343-6.
• Tudek B, Van Zeeland AA, Kusmierek JT, Laval J. (1998) Mutat Res. ; 407: 169-76.