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Polymorphic genes for the peroxide scavenger glutathione peroxidase I (GPX1) and 8-hydroxydeoxyguanosine (8-OHdG) DNA glycosylase/apurinic (AP) lyase (hOGG1) map to loci on chromosome 3p which are subject to frequent loss of heterozygosity (LOH) in lung tumours. Levels of the pro-mutagenic, oxidative DNA lesion 8-OHdG, were measured in 37 paired normal and tumorous lung specimens using HPLC with electrochemical detection. Lung tumours were also analysed for 3p LOH by fluorescent PCR with Genescan analysis. No significant difference was observed between 8-OHdG levels in tumour [7.7 ± 6.7 (mean ± SE) 8-OHdG/106 2′-deoxyguanosine (dG)] and normal (8.1 ± 8.8 8-OHdG/106 dG) lung tissue. Adduct levels in normal lung tissue DNA were not associated with constitutive hOGG1 genotype although there was a trend towards lower 8-OHdG levels in individuals possessing the ALA6 GPX1 polymorphism. Lung tumours exhibiting 3p LOH (40%) contained higher levels of 8-OHdG adducts (10.9 ± 2.6 8-OHdG/106 dG) (P = 0.05) and lower GPX1 enzyme activity [45.5 nmol glutathione (GSH)/min/mg] (P = 0.09) when compared with tumours without LOH at these sites (5.55 ± 0.87 8-OHdG/106 dG and 63.6 nmol GSH/min/mg, respectively). In conclusion, tumours with 3p LOH at loci associated with hOGG1 and GPX1 appear to have compromised oxidative defence mechanisms as measured by reduced GPX1 enzyme activity and elevated 8-OHdG levels and this may affect the prognosis of lung cancer patients. [ABSTRACT FROM PUBLISHER]

Aims: The sharp increase in the incidence of oesophageal adenocarcinoma over a relatively short period of time indicates that environmental factors are involved in the aetiology and epidemiological data suggest that dietary antioxidants might have a protective effect against the development of the disease. The aim of this study was to measure tissue and plasma levels of vitamin C and ascorbic acid in patients with Barrett's oesophagus. Methods: Blood samples and endoscopic biopsies from squamous, Barrett's, and gastric mucosa were obtained from consecutive patients participating in a surveillance programme. Vitamin levels were measured by high performance liquid chromatography and mean values were compared by a two-tailed unpaired t-test. Results: Forty-two male and 15 female volunteers were recruited. Histology of the Barrett's epithelium revealed nine cases with gastric metaplasia, 45 with intestinal metaplasia and three with dysplasia. The mean values ± SD) of ascorbic acid in squamous, Barrett's and gastric mucosa were 111.1 (± 51.1), 86.9 (± 38) and 75.8 (± 35.8) µg g[sup -1], respectively. The difference between the mean values in squamous and Barrett's mucosa was statistically significant (P = 0.02). The difference between Barrett's and gastric mucosa was not significant. There was also a statistically significant difference between the mean plasma levels of ascorbic acid in male [mean = 7.51 (± 3.7) µg mL[sup -1]] and female [mean = 10.14 (± 4.2) µg mL[sup -1] patients (P = 0.04). A trend towards a decrease in the mean plasma levels of ascorbic acid was noted between patients with gastric metaplasia, intestinal metaplasia and dysplasia (10.57 versus 7.98 versus 4.56 µg mL[sup -1]) but this failed to reach statistical significance due to the small number of patients in each subgroup. Similar results were obtained for the tissue and plasma levels of vitamin C. Conclusions: These results suggest... [ABSTRACT FROM AUTHOR]