Benzo[a]pyrene diol-epoxide-I-DNA and oxidative DNA adducts associated with gastric adenocarcinoma.
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.
Lee
B M
BM
Division of Toxicology, College of Pharmacy, Sung Kyun Kwan University, Suwon, South Korea. bmlee@yurim.skku.ac.kr
Jang
J J
JJ
Kim
H S
HS
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis*; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000378:metabolism*
D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine