Oxidative DNA damage in cancer patients: a cause or a consequence of the disease development?
A wide variety of oxidative DNA lesions are present in living cells. One of the best known lesions of this type is 8-oxoguanine (8-oxoGua) which has been shown to have mutagenic properties. An influence of antioxidative vitamins and labile iron pool on the background level of 8-oxoGua in cellular DNA is discussed and oxidative damage to free nucleotide pool as a possible source of 8-oxo-2'-deoxyguanosine in DNA and urine is described. An involvement of 8-oxoGua in the origin and/or progression of cancer is reviewed. It is concluded that a severe oxidative stress manifested as a high level of 8-oxoGua in cellular DNA as well as in urine of cancer patients is a consequence of development of many types of cancer. Although at present it is impossible to answer directly the question concerning involvement of oxidative DNA damage in cancer etiology it is likely that oxidative DNA base modifications may serve as a source of mutations that initiate carcinogenesis (i.e. they may be causal factors responsible for the process).
Olinski
Ryszard
R
Department of Clinical Biochemistry, The Ludwik Rydygier Medical University in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland. ryszardo@amb.bydgoszcz.pl
Gackowski
Daniel
D
Rozalski
Rafal
R
Foksinski
Marek
M
Bialkowski
Karol
K
D002273:Carcinogens / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology*; D018384:Oxidative Stress
D002273:Carcinogens; C024829:8-hydroxyguanine; D006147:Guanine; D007501:Iron; D003849:Deoxyguanosine