Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali.

Background: Hepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers.

Methods: A group of 1466 adult volunteers was recruited in the district of Bamako.

Association between TP53 R249S mutation and polymorphisms in TP53 intron 1 in hepatocellular carcinoma.

Over 100 single nucleotide polymorphisms (SNP) are validated in the TP53 tumor suppressor gene. They define haplotypes, which may differ in their activities. Therefore, mutation in cancer may occur at different rates depending upon haplotypes.

Association between HBX status, aflatoxin-induced R249S TP53 mutation and risk of hepatocellular carcinoma in a case-control study from Thailand.

Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) chronicity and dietary exposure to aflatoxin, a mutagen targeting codon 249 of tumor suppressor TP53 (R249S mutation). Based on a case-control in Thailand, we have measured R249S and the status of HBX gene in plasma DNA of 176 cases and 133 referents. Detection of HBX complete sequences was associated with R249S in HCC with no documented prior cirrhosis but not in HCC developing in a context of cirrhosis or in non-cancer chronic liver diseases.

Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study.

Background: The lack of association found in several cohort studies between dietary saturated fat and coronary heart disease (CHD) risk has renewed debate over the link between dietary fats and CHD.

Methods And Findings: We assessed the relationship between plasma phospholipid fatty acid (PFA) concentration and incident CHD using a nested case control design within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40-79 years examined in 1993-1997 and followed up to 2009. Plasma PFA concentrations were measured by gas chromatography in baseline samples retrieved from frozen storage.

Serum α-tocopherol and γ-tocopherol concentrations and prostate cancer risk in the PLCO Screening Trial: a nested case-control study.

Background: Vitamin E compounds exhibit prostate cancer preventive properties experimentally, but serologic investigations of tocopherols, and randomized controlled trials of supplementation in particular, have been inconsistent. Many studies suggest protective effects among smokers and for aggressive prostate cancer, however.

Methods: We conducted a nested case-control study of serum α-tocopherol and γ-tocopherol and prostate cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, with 680 prostate cancer cases and 824 frequency-matched controls.

TP53 R249S mutation, genetic variations in HBX and risk of hepatocellular carcinoma in The Gambia.

In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B(1) (AFB(1)) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population.

Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis.

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases.

Simultaneous quantification of steroids in rat intratesticular fluid by HPLC-isotope dilution tandem mass spectrometry.

An isotope dilution mass spectrometry method has been developed for the simultaneous measurement of picolinoyl derivatives of testosterone (T), dihydrotestosterone (DHT), 17β-estradiol (E(2)), and 5α-androstan-3α,17β-diol (3α-diol) in rat intratesticular fluid. The method uses reversed-phase high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. Following derivatization of 10-μL samples of testicular fluid with picolinoyl chloride hydrochloride, the samples were purified by solid phase extraction before analysis.

Seasonal variation in TP53 R249S-mutated serum DNA with aflatoxin exposure and hepatitis B virus infection.

Background: Chronic hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) exposure are etiological factors for hepatocellular carcinoma (HCC) in countries with hot, humid climates. HCC often harbors a TP53 (tumor protein p53) mutation at codon 249 (R249S). In chronic carriers, 1762T/1764A mutations in the HBV X gene are associated with increased HCC risk.

Bioavailability of Sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China.

One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout-derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR.

Insulin-like growth factor-II methylation status in lymphocyte DNA and colon cancer risk in the Northern Sweden Health and Disease cohort.

Loss of imprinting (LOI) of the insulin-like growth factor II (IGFII) gene is a frequent phenomenon in colorectal tumor tissues. Previous reports indicated that subjects with colorectal neoplasias show LOI of IGFII in circulating lymphocytes. Furthermore, LOI of IGFII is strongly related to the methylation of a differentially methylated region (DMR) in intron 2 of IGFII, suggesting that the methylation status could serve as a biomarker for early detection.

Serum retinol and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial.

Vitamin A (retinol) plays a key role in the regulation of cell growth and differentiation, and has been studied as a potential chemopreventive agent for prostate cancer. However, findings from epidemiologic studies on the association between circulating retinol concentrations and the risk of prostate cancer are inconsistent. We examined whether serum concentrations of retinol were associated with the risk of prostate cancer in a nested case-control study using 692 prostate cancer cases and 844 matched controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Transgenic expression of aflatoxin aldehyde reductase (AKR7A1) modulates aflatoxin B1 metabolism but not hepatic carcinogenesis in the rat.

In both experimental animals and humans, aflatoxin B(1) (AFB(1)) is a potent hepatic toxin and carcinogen against which a variety of antioxidants and experimental or therapeutic drugs (e.g., oltipraz, related dithiolethiones, and various triterpenoids) protect from both acute toxicity and carcinogenesis.

Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry.

We report validation of the first high-pressure liquid chromatography isotope-dilution mass spectrometry method to measure sulforaphane (SFN) and its glutathione-derived conjugates in human urine. As epidemiological evidence continues to mount that the consumption of a diet rich in cruciferous vegetables may reduce the risk of certain cancers, the development of analytical methodologies to accurately measure isothiocyanates (ITCs) and their subsequent metabolic products becomes paramount. SFN, the principal ITC produced by broccoli, is an effective chemopreventive agent with multiple modes of action.

Formation of two novel estrogen guanine adducts and HPLC/MS detection of 4-hydroxyestradiol-N7-guanine in human urine.

Estrogen-DNA adducts are potential biomarkers for assessing the risk of developing of a number of hormonally modified cancers, including breast cancer. Formation of the 4-hydroxyestradiol-N(7)-guanine (4-OHE2-N(7)-guanine) adduct from the reaction of estradiol-3,4-quinone with DNA and its detection in vivo has been established. With the ultimate goal of exploring estrogen-DNA adducts as biomarkers in experimental and human investigations, the 4-OHE2-N(7)-guanine was synthesized, and preliminary studies demonstrated that this adduct was detectable in all 10 female human urine samples examined.

Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial.

Background: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive.

Dietary fish intake and plasma phospholipid n-3 polyunsaturated fatty acid concentrations in men and women in the European Prospective Investigation into Cancer-Norfolk United Kingdom cohort.

Background: The n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid and eicosapentaenoic acid, found in fish and fish-oil supplements and also formed by conversion of alpha-linolenic acid in soy and rapeseed (canola) oils, are thought to have cardioprotective effects.

Objective: Because the relative feasibility and measurement error of dietary methods varies, this study compared fish and fish-oil intakes obtained from 4 dietary methods with plasma n-3 PUFAs in men and women in a general population.

Design: The study participants were 4949 men and women aged 40-79 y from the European Prospective Investigation into Cancer-Norfolk United Kingdom cohort.

Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance liquid chromatography and isotope dilution tandem mass spectrometry.

We report validation of the first isotope dilution mass spectrometry method for determination of aflatoxin B(1)-N(7)-guanine (AFB(1)-N(7)-Gua), a major human aflatoxin-DNA adduct that is excreted in the urine. Measurement of urinary AFB(1)-N(7)-Gua, a biomarker of the biologically effective dose following dietary aflatoxin B(1) (AFB(1)) exposure, has helped identify AFB(1) as a risk factor in the development of hepatocellular carcinoma, a common cancer worldwide. Triple-quadrupole mass spectrometry, coupled with the use of a stable isotope-labeled internal standard (AFB(1)-N(7)-(15)N(5)-Gua) and better solid phase extraction and immunoaffinity column chromatography, have enabled us to greatly improve accuracy, precision, specificity, and sensitivity over previously published determinations.

Quantitative comparison of aflatoxin B1 serum albumin adducts in humans by isotope dilution mass spectrometry and ELISA.

Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B(1) (AFB(1)) results in the covalent attachment of AFB(1) to serum albumin. Digestion of adducted albumin releases AFB(1)-lysine, a biomarker of exposure status. AF-albumin adducts have been most frequently measured in precipitated serum albumin using an immunoassay (ELISA); however, a sensitive and specific isotope dilution mass spectrometric (IDMS) assay for measurement of AFB(1)-lysine in serum has recently been developed.

Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry.

A mutation in codon 249 of the TP53 gene (249(Ser)), related to aflatoxin B(1) exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal standard plasmid, plasma concentrations of 249(Ser)-mutated DNA were quantified by electrospray ionization mass spectrometry in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249(Ser) (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; interquartile range: 500-2,000; P < 0.

Long-term cryoconservation and stability of vitamin C in serum samples of the European prospective investigation into cancer and nutrition.

Plasma vitamin C level may be associated with risk of some chronic diseases. The rapid degradability of vitamin C in biological samples necessitates its stabilization with metaphosphoric acid or similar agents. However, in most cohort studies, prospectively collected biological samples are not treated with stabilizing agents before long-term frozen storage and it is not known whether vitamin C can be properly measured in such samples.

Nitration and nitrosation of N-acetyl-L-tryptophan and tryptophan residues in proteins by various reactive nitrogen species.

Proteins are targets of reactive nitrogen species such as peroxynitrite and nitrogen dioxide. Among the various amino acids in proteins, tryptophan residues are especially susceptible to attack by reactive nitrogen species. We carried out experiments on the reactions of peroxynitrite and other reactive nitrogen species with N-acetyl-L-tryptophan under various conditions.

Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa.

Hepatocellular carcinoma (HCC) is frequent in areas of high exposure to aflatoxin and high prevalence of HBV infection, such as western Africa and south-east China. A selective mutation in TP53 (AGG-->AGT at codon 249, Arg-->Ser) has been identified as a hotspot in HCCs from such areas, reflecting DNA damage caused by aflatoxin metabolites. Recent studies have shown that circulating free DNA can be retrieved from human plasma, and it is hypothesised that plasma DNA may serve as a source for biomarkers of tumorigenic processes.

Sensitive and specific detection of K-ras mutations in colon tumors by short oligonucleotide mass analysis.

Short oligonucleotide mass analysis (SOMA) is a technique by which small sequences of mutated and wild-type DNA, produced by PCR amplification and restriction digestion, are characterized by HPLC-electrospray ionization tandem mass spectrometry. We have adapted the method to specifically detect two common point mutations at codon 12 of the c-K-ras gene. Mutations in DNA from 121 colon tumor samples were identified by SOMA and validated by comparison with sequencing.

Idiopathic and radiation-induced ocular telangiectasia: the involvement of the ATM gene.

Purpose: To investigate whether individuals, with no family history of ataxia telangiectasia (AT), in whom idiopathic or radiation-induced ocular telangiectasia developed are carriers of ATM gene mutations.

Methods: The ATM cDNA from lymphoblastoid cell lines established from 16 patients with idiopathic retinal or choroidal telangiectasia and 14 patients with radiation-induced telangiectasia after radiotherapy for age-related macular degeneration (AMD) was screened using the restriction endonuclease fingerprinting technique. The frequency of each detected variant was determined in the French population by either a mass spectrometry-based technique or variant-specific endonuclease digestion.