Base excision repair activities differ in human lung cancer cells and corresponding normal controls

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Oxidative damage to DNA is thought to play a role in carcinogenesis by causing mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway for the repair of oxidized modifications both in nuclear and mitochondrial DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three cell lines used. However, the specific activities and cancer versus control comparison differed significantly between the nuclear and mitochondrial compartments. OGG1 activity, as measured by 8-oxodA incision, was up-regulated in cancer cell mitochondria but down-regulated in the nucleus when compared to control cells. Similarly, NTH1 activity was also up-regulated in mitochondrial extracts from cancer cells but did not change significantly in the nucleus. Together, these results support the idea that alterations in BER capacity are associated with carcinogenesis.
Original languageEnglish
JournalAnticancer Research
Issue number12
Pages (from-to)4963-71
Number of pages9
Publication statusPublished - 1 Dec 2010

    Research areas

  • Cell Line, Tumor, Cell Nucleus, Cell Transformation, Neoplastic, DNA Damage, DNA Glycosylases, DNA Repair, DNA, Mitochondrial, DNA, Neoplasm, DNA-(Apurinic or Apyrimidinic Site) Lyase, Deoxyribonuclease (Pyrimidine Dimer), Genomic Instability, Humans, Lung Neoplasms, Mitochondria, Uracil-DNA Glycosidase

ID: 33492796