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Deoxynivalenol (DON) is a ubiquitous contaminant of cereal crops in temperate regions of the world. It causes growth faltering and immune suppression in animals. Limited information is available on DON exposure in UK subpopulations. The objective of this study was to provide DON exposure assessment in a subset of pregnant women scheduled for an elective caesarean in a large multi-ethnic mother/infant birth cohort from Bradford, UK. Women aged 16–44 years (n = 85) provided a urine sample for DON analysis in the last trimester of pregnancy, and concurrently completed a food-frequency questionnaire (FFQ). The urinary DON biomarker was detected in all measured samples (geometric mean (GM) = 10.3 ng DON mg−1 creatinine, range = 0.5−116.7 ng mg−1). Levels were higher in women classified as South Asian in origin (GM: 15.2 ng mg−1; 95% CI = 10.7−21.5 ng mg−1) compared with non-South Asians (GM = 8.6 ng mg−1; 95% CI = 6.6−11.8 ng mg−1), p = 0.02). Estimated DON intake from FFQ data and typical levels of DON contamination of food suggest that this was mainly due to higher levels of exposure from bread, particularly daily intake of DON from chapattis in South Asians (estimated mean = 2.4 µg day−1; 95% CI = 1.2, 3.7 µg day−1) compared with non-South Asians (estimated mean = 0.2 µg day−1; 95% CI = 0−0.4 µg day−1), p < 0.001. This is the first biomarker demonstration of DON exposure in pregnant women, and several urinary DON levels were the highest ever recorded in any study. A larger survey within this birth cohort is warranted to investigate any potential risk to mothers and their babies, from DON exposure during pregnancy. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a trichothecene mycotoxin found on wheat, maize and barley. In ecological surveys in China, DON and other trichothecenes have been implicated in acute poisoning episodes and linked with the incidence of esophageal cancer. In order to better understand exposure patterns, this pilot survey provided a combined measure of urinary un-metabolised or free DON (fD) and its glucuronide metabolite (DG) in a subset of 60 samples taken from the Shanghai Women's Health Study cohort, China. Samples were collected in 1997/1998 from women age 40–70 years. Urinary fD+DG combined was detected in 58/60 (96.7%) samples (mean 5.9 ng DON/mg creatinine; range nd – 30.5); a similar frequency, and a mean level approximately half, of that previously observed for women in the UK. Wheat consumption was approximately 25% of that consumed by western diets; thus DON contamination of wheat may be higher in Shanghai than the UK. The de-epoxy metabolite of DON, a detoxification product observed in animals, was not detected, suggesting that humans may be particularly sensitive to DON due to a more restricted detoxification capacity. [ABSTRACT FROM AUTHOR]

Barrett's oesophagus (BE) is a pre-malignant metaplastic tissue predisposing to oesophageal adenocarcinoma (EC), and gastro-oesophageal reflux is a risk factor for both conditions. Reflux of acid and bile can cause mucosal injury and initiate chronic inflammation. These processes can induce DNA damage, possibly via an oxidative stress mechanism, thus increasing the likelihood of progression from Barrett's metaplasia to dysplasia and finally carcinoma. The comet assay was optimized for the detection of DNA damage (strand breaks and alkali-labile sites) in oesophageal biopsies, including incorporation of the DNA repair enzyme Fapy-DNA glycosylase (Fpg). Fpg allows the detection of 8-hydroxy-2-deoxyguanosine (8-OHdG) sites, a known pro-mutagenic DNA lesion. BE patients were recruited from BE surveillance clinics and oesophageal biopsies collected at endoscopy. Comet analysis revealed significantly increased ( p <0.001) DNA damage in Barrett's epithelium compared with matched squamous epithelium, with median % tail DNA values of 25.1% (first to third quartile 21.7-29.6%) and 18.6% (first to third quartile 16.9-21.4%), respectively. The median % tail DNA was up to 70% higher in the matched BE tissue compared with squamous epithelium from the same patient. Fpg sensitive sites were demonstrated in both tissue types at similar levels. The raised level of DNA damage in the premalignant BE may contribute to the accumulation of genetic alterations occurring during progression to EC. Understanding these underlying mechanisms provides a basis for cancer prevention strategies in BE patients. [ABSTRACT FROM AUTHOR]

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]

Chromoendoscopy with methylene blue (MB) is increasingly being applied during endoscopic examination of Barrett's oesophagus (BO). MB selectively stains specialised intestinal metaplasia as it is specifically absorbed by the goblet cells characterising this tissue. Experimental studies show that photosensitisation of MB with visible light stimulates the formation of singlet oxygen species leading to the generation of single strand breaks and oxidative alterations to guanine residues of which the promutagenic DNA adduct, 8-hydroxydeoxyguanosine (8-OHdG) predominates. We hypothesised that the application of MB to the oesophagus followed by exposure to endoscopic light may stimulate high levels of DNA damage in BO. Biopsies were collected before and after MB exposure from immediately adjacent sites within BO mucosa from 15 patients. Biopsies were subject to DNA damage analysis using the comet assay to detect strand breaks and alkali-labile sites. In addition the enzyme Fapy-DNA glycosylase (FpG) was incorporated into the assay to allow the detection of FpG sensitive sites, including 8-OHdG. For every patient studied, DNA damage levels increased (range 6.0-71.9%) following MB chromoendoscopy. Statistical comparison of matched biopsies revealed a significant difference (p < 0.005) in the DNA damage level before (28.8% (24.6-32.4%), median percentage tail DNA (1st-3rd quartile)) compared to after chromoendoscopy (36.5% (32.1-42.7%)). Following MB chromoendoscopy the percentage of cells with highly damage DNA attributable to FpG sensitive sites, approximately doubled. Barrett's mucosa is a recognised preneoplastic tissue, which exhibits many genetic and epigenetic alterations. Exposing this and any associated dysplasia to further promutagenic DNA damage, via MB chromoendoscopy warrants caution as it could potentially accelerate the carcinogenic process. [ABSTRACT FROM AUTHOR]

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]