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Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Benzo[a]pyrene diol-epoxide-I-DNA and oxidative DNA adducts associated with gastric adenocarcinoma
1Division of Toxicology, College of Pharmacy, Sung Kyun Kwan University, Suwon, South Korea. bmlee@yurim.skku.ac.kr
Abstract:
BPDE-I-DNA and oxidative DNA adducts (8-OHdG) were investigated in stomach tissues (tumor and tumor-adjacent) of patients (N = 211) with gastric adenocarcinoma and in normal stomach tissues (N = 113). In each stomach specimen, the levels of BPDE-I-DNA adducts were quantitatively measured by enzyme linked immunosorbent assay (ELISA) and oxidative DNA damage was measured by HPLC-ECD. Higher levels of total BPDE-I-DNA adduct were observed in tumor (4.20 +/- 0.59 fmol/microg DNA) and tumor-adjacent (3.68 +/- 0.62 fmol/microg DNA) tissues than in normal stomach tissues (2.80 +/- 0.53 fmol/microg DNA) but were not significant. In males, BPDE-I-DNA adduct was significantly higher in tumor tissues (4.25 +/- 0.42 fmol/microg DNA) than in normal tissues (2.83 +/- 0.59 fmol/microg DNA) (P < 0.05). In smokers, BPDE-I-DNA adduct was slightly higher in tumor tissues (4.92 +/- 0.82 fmol/microg DNA) than in tumor-adjacent tissues (3.99 +/- 0.92 fmol/microg DNA). Gastric cancer patients had significantly higher levels of 8-OHdG in their tumor-adjacent (7.54 +/- 0.43 residues/10(5) dG) and tumor tissues (6.29 +/- 0.39 residues/10(5) dG) than in normal tissues (2.86 +/- 0.11 residues/10(5) dG) (P < 0.001). Smokers showed higher levels of 8-OHdG in both tumor (6.44 +/- 0.62 residues/10(5) dG) and tumor-adjacent (8.12 +/- 0.68 residues/10(5) dG) tissues than in non-smokers (5.80 +/- 0.47 and 7.11 +/- 0.57 residues/10(5) dG, respectively). 8-OHdG levels were significantly increased in positive tissues with Helicobacter pylori (H. pylori) infection compared with negative tissues (P < 0.01). Also, the frequency of H. pylori infection was higher in tumor-adjacent tissues (73%) than in tumor (42%) or normal tissues (44%). These results demonstrate that there are higher levels of 8-OHdG and BPDE-I-DNA adducts in tumor and tumor-adjacent tissues than in normal tissues and that these higher levels might be related to gastric tumorigenesis, although benzo[a]pyrene could be a minor contributing component in the environment.
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