Involvement of oxidatively damaged DNA and repair in cancer development and aging - PubMed (original) (raw)

. 2010 May 15;2(3):254-84.

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Involvement of oxidatively damaged DNA and repair in cancer development and aging

Barbara Tudek et al. Am J Transl Res. 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 in the development and pathology of an organism, 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 lesions 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 directly answer 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 these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities.

Keywords: 1,N6-ethenoadenine; 3,N4-ethenocytosine; 8-oxoguanine; DNA repair; carcinogenesis; polymorphism.

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Figures

Figure 1

Figure 1

Major base lesions induced in DNA by oxidative stress and lipid peroxidation

Figure 2

Figure 2

“GO” system

Figure 3

Figure 3

Base excision activity toward ethenoadducts: (A,C) εA; (B,D) εC in lung cancer patients. SQ squamous cell carcinoma; AD – adenocarcinoma.

Figure 4

Figure 4

Examples of HNE and its epoxide adducts to deoxyguanosine.

Figure 5

Figure 5

The mean level of 8-oxodG in leukocyte DNA in different age groups.

Figure 6

Figure 6

Correlation between the level of 8-oxodG in leukocyte DNA and age with exclusion of group A.

Figure 7

Figure 7

The mean levels of 8-oxoGua (A) and 8-oxodG (B) in urine in the different age groups.

Figure 8

Figure 8

Relationship between the level of vitamin C and age in all studied subjects.

Figure 9

Figure 9

Relationship between the urinary excretion rates of the analyzed modifications and specific metabolic rates (SMR) of six different mammalian species.

Figure 10

Figure 10

Relationship between the urinary excretion rates of the analyzed modifications and natural logarithm of maximum life span (MLSP) of six different mammalian species.

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