Age-related changes in oxidative DNA damage and benzo(a)pyrene diolepoxide-I (BPDE-I)-DNA adduct levels in human stomach.
This study was conducted in order to obtain information on the association between age and oxidative DNA damage and benzo[a]pyrene diolepoxide-I (BPDE-I)-DNA adduct levels in the stomach tissues of normal subjects (n = 113). Subjects ranged from 17 to 75 yr. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were measured by high-performance liquid chromatography-electrochemical detector (HPLC-ECD). BPDE-I-DNA adduct levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA) using the monoclonal antibody 8E11. Increase in 8-OHdG levels was observed in subjects from 31 to 60 yr of age. Higher levels of 8-OHdG were observed in the stomach tissues of those in the 51-60 yr old group. Although Helicobacter. Pylori-positive group subjects had higher 8-OHdG levels than those in the H. pylori-negative group, no age-related changes in 8-OHdG levels were observed in these groups. The levels of BPDE-I-DNA adduct also markedly increased with age. Higher levels of BPDE-I-DNA adduct were observed in subjects aged 61-70 yr, but this difference was not significant from other age groups. These results provide evidence that there is a progressive age-dependent accumulation of oxidative DNA damage and of BPDE-I-DNA adducts in human stomach tissues. It is possible that such damage contributes to the known increased incidence of gastric tumor with aging.
Lee
Byung Mu
BM
Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Changan-Ku, Kyunggi-Do, Suwon.
Kwack
Seung Jun
SJ
Kim
Hyung Sik
HS
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001580:Benzopyrenes / Q000378:metabolism*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000378:metabolism*
D001580:Benzopyrenes; 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; C072019:benzo(a)pyrene diolepoxide I; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine