Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7 ' 8-dihydro-2 '-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker
Por:
Borrego, S, Vazquez, A, Dasi, F, Cerda, C, Iradi, A, Tormos, C, Sanchez, J, Bagan, L, Boix, J, Zaragoza, C, Camps, J and Saez, G
Publicada:
1 feb 2013
Resumen:
We characterized the oxidative stress (OS) status by the levels of reduced/oxidized glutathione (GSH/GSSG), malondialdehyde (MDA) and the mutagenic base 8-oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) in human gastric carcinoma (HGC) samples and compared the results with normal tissue from the same patients. We also analyzed 8-oxo-dG in peripheral mononuclear cells (PMNC) and urine from healthy control subjects and in affected patients in the basal state and one, three, six, nine and twelve months after tumor resection. The levels of DNA repair enzyme mRNA expression (hOGG1, RAD51, MUYTH and MTH1) were determined in tumor specimens and compared with normal mucosa. Tumor specimens exhibited increased levels of MDA and 8-oxo-dG compared with normal gastric tissue. GSH levels were also increased, while GSSG levels remained stable. DNA repair enzyme mRNA expression was induced in the tumor tissues. Levels of 8-oxo-dG were significantly elevated in both urine and PMNC of gastric cancer patients compared with healthy controls. After gastrectomy, the levels of the damaged base in urine and PMNC decreased progressively to values close to those found in the healthy population. The high levels of 8-oxo-dG in urine may be related to the increased induction of DNA repair activity in tumor tissue, and the changes observed after tumor resection support its potential use as a tumor marker.
Filiaciones:
Borrego, S:
CDB Gen Univ Hosp, Clin Anal Serv, Valencia 46014, Spain
SEQC, Oxidat Stress Res Grp, Barcelona 08025, Spain
Vazquez, A:
Gen Univ Hosp, Dept Gen Surg & Digest Dis, Valencia 46014, Spain
Dasi, F:
Valencia Clinical Hosp Res Fdn INCLIVA, Valencia 46010, Spain
Cerda, C:
CDB Gen Univ Hosp, Clin Anal Serv, Valencia 46014, Spain
SEQC, Oxidat Stress Res Grp, Barcelona 08025, Spain
Iradi, A:
Univ Valencia, Fac Med, Dept Physiol, Valencia 46010, Spain
Tormos, C:
Univ Valencia, Fac Med, Dept Biochem & Mol Biol, Valencia 46010, Spain
Sanchez, J:
Univ Valencia, Fac Med, Dept Biochem & Mol Biol, Valencia 46010, Spain
Bagan, L:
Univ Valencia, Fac Med, Dept Biochem & Mol Biol, Valencia 46010, Spain
Boix, J:
Univ Valencia, Fac Med, Dept Pathol, Valencia 46010, Spain
Zaragoza, C:
Gen Univ Hosp, Dept Gen Surg & Digest Dis, Valencia 46014, Spain
Camps, J:
Univ Rovira & Virgili, Hlth Inst Res Pere Virgili, St Joan Univ Hosp, Bimed Res Ctr, E-43201 Reus, Spain
:
CDB Gen Univ Hosp, Clin Anal Serv, Valencia 46014, Spain
SEQC, Oxidat Stress Res Grp, Barcelona 08025, Spain
Univ Valencia, Fac Med, Dept Biochem & Mol Biol, Valencia 46010, Spain
Green Published, gold, Green Submitted
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