Benzo[ a]pyrene diol-epoxide-I-DNA and oxidative DNA adducts associated with gastric adenocarcinoma

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/ μg DNA) and tumor-adjacent (3.68±0.62 fmol/ μg DNA) tissues than in normal stomach tissues (2.80±0.53 fmol/ μg DNA) but were not significant. In males, BPDE-I-DNA adduct was significantly higher in tumor tissues (4.25±0.42 fmol/ μg DNA) than in normal tissues (2.83±0.59 fmol/ μg DNA) ( P<0.05). In smokers, BPDE-I-DNA adduct was slightly higher in tumor tissues (4.92±0.82 fmol/ μg DNA) than in tumor-adjacent tissues (3.99±0.92 fmol/ μg 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.