The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours.
OBJECTIVE
The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamous mucosa.


METHODS
We measured 8-OHdG in 51 patients (13 Barrett's metaplasia, six Barrett's oesophagus with high-grade dysplasia, 18 adenocarcinoma of the distal oesophagus/oesophagogastric junction and 14 normal controls). The amount of DNA damage was determined by high-performance liquid chromatography in oesophagus samples obtained either from endoscopy or as samples from surgery. The median 8-OHdG concentration was expressed as the ratio of 8-OHdG per 10(5) deoxyguanosine.


RESULTS
Analysis revealed that 8-OHdG was present in both Barrett's metaplasia with and without dysplasia as well as in adenocarcinoma of the oesophagus/oesophagogastric junction. Although the study group was small the amount of 8-OHdG was significantly increased in the distal oesophagus both in Barrett's epithelium 1.26 (0.08-29.47) and in high-grade dysplasia 1.35 (1.04-1.65) as well as in adenocarcinoma of oesophagus/oesophagogastric junction 1.08 (0.59-1.94) compared to controls 0.06 (0-4.08) (p=0.002, p=0.012, p=0.001, respectively). Barrett's patients had no significant difference in 8-OHdG levels between their distal and proximal oesophageal samples.


CONCLUSIONS
Our results show the presence of oxidative DNA damage in the distal oesophagus of patients with Barrett's oesophagus and adenocarcinoma of the oesophagus/oesophagogastric junction. This may have a connection to carcinogenesis in Barrett's oesophagus.
Räsänen
J V
JV
Division of General Thoracic and Oesophageal Surgery, Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 340, FIN-00029 HUS, Helsinki, Finland.
Sihvo
E I T
EI
Ahotupa
M O
MO
Färkkilä
M A
MA
Salo
J A
JA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000378:metabolism*; D004943:Esophagogastric Junction / Q000378:metabolism / Q000473:pathology; D004945:Esophagoscopy; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine