Base excision repair activities differ in human lung cancer cells and corresponding normal controls
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Base excision repair activities differ in human lung cancer cells and corresponding normal controls. / Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C.
In: Anticancer Research, Vol. 30, No. 12, 01.12.2010, p. 4963-71.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Base excision repair activities differ in human lung cancer cells and corresponding normal controls
AU - Karahalil, Bensu
AU - Bohr, Vilhelm A
AU - De Souza-Pinto, Nadja C
PY - 2010/12/1
Y1 - 2010/12/1
N2 - 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.
AB - 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.
KW - Cell Line, Tumor
KW - Cell Nucleus
KW - Cell Transformation, Neoplastic
KW - DNA Damage
KW - DNA Glycosylases
KW - DNA Repair
KW - DNA, Mitochondrial
KW - DNA, Neoplasm
KW - DNA-(Apurinic or Apyrimidinic Site) Lyase
KW - Deoxyribonuclease (Pyrimidine Dimer)
KW - Genomic Instability
KW - Humans
KW - Lung Neoplasms
KW - Mitochondria
KW - Uracil-DNA Glycosidase
M3 - Journal article
C2 - 21187477
VL - 30
SP - 4963
EP - 4971
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 12
ER -
ID: 33492796