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Am J Translational Res 2010;2(3):254-284
Review Article
Involvement of oxidatively damaged DNA and repair in cancer
development and aging
Barbara Tudek, Alicja Winczura, Justyna Janik, Agnieszka Siomek, Marek Foksinski, Ryszard Oliński
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Institute of Genetics and
Biotechnology, Warsaw University, Poland, Postgraduate School of Molecular Medicine, Warsaw, Poland
Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
Received April 1, 2010, accepted May 6, 2010, available online May 15, 2010
Abstract: DNA damage and DNA repair may mediate several cellular processes, like replication and
transcription, mutagenesis and apoptosis and thus may be important factors for the organism development and
pathology, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen
species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA
bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is
one of the best known DNA damage due to its mutagenic properties. Among LPO-derived DNA base
modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions
considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible
to answer directly the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely
that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are
involved in aging (i.e. they may be causal factors responsible for the processes). To counteract the deleterious
effect of oxidatively damaged DNA, all organisms developed several DNA repair mechanisms. It was observed
that the repair efficiency of oxidatively damaged DNA is frequently decreased in cancer patients. The present work
reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and
ethenoadducts occurrence in DNA in aspect of cancer development, drawing attention to the multiplicity of
proteins with repair activities. (AJTR1004001).
Key words: 8-oxoguanine, 1,N6-ethenoadenine, 3,N4-ethenocytosine, DNA repair, polymorphism,
carcinogenesis
Full Text PDF
Address all correspondence to:
Ryszard Olinski, MD
Department of Clinical Biochemistry
Collegium Medicum Nicolaus Copernicus University
ul. Karlowicza 24, PO-85-092 Bydgoszcz, Poland
Tel +48 52 585 37 70 and +48 52 585 37 44
Fax +48 52 585 37 71
E-mail: ryszardo@cm.umk.pl
Review Article
Involvement of oxidatively damaged DNA and repair in cancer
development and aging
Barbara Tudek, Alicja Winczura, Justyna Janik, Agnieszka Siomek, Marek Foksinski, Ryszard Oliński
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Institute of Genetics and
Biotechnology, Warsaw University, Poland, Postgraduate School of Molecular Medicine, Warsaw, Poland
Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
Received April 1, 2010, accepted May 6, 2010, available online May 15, 2010
Abstract: DNA damage and DNA repair may mediate several cellular processes, like replication and
transcription, mutagenesis and apoptosis and thus may be important factors for the organism development and
pathology, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen
species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA
bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is
one of the best known DNA damage due to its mutagenic properties. Among LPO-derived DNA base
modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions
considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible
to answer directly the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely
that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are
involved in aging (i.e. they may be causal factors responsible for the processes). To counteract the deleterious
effect of oxidatively damaged DNA, all organisms developed several DNA repair mechanisms. It was observed
that the repair efficiency of oxidatively damaged DNA is frequently decreased in cancer patients. The present work
reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and
ethenoadducts occurrence in DNA in aspect of cancer development, drawing attention to the multiplicity of
proteins with repair activities. (AJTR1004001).
Key words: 8-oxoguanine, 1,N6-ethenoadenine, 3,N4-ethenocytosine, DNA repair, polymorphism,
carcinogenesis
Full Text PDF
Address all correspondence to:
Ryszard Olinski, MD
Department of Clinical Biochemistry
Collegium Medicum Nicolaus Copernicus University
ul. Karlowicza 24, PO-85-092 Bydgoszcz, Poland
Tel +48 52 585 37 70 and +48 52 585 37 44
Fax +48 52 585 37 71
E-mail: ryszardo@cm.umk.pl
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