Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan.

School of Public Health, National Defense Medical Center, School of Public Health, No. 161, Section 6, Min-Chuan East Road, Taipei 114, Taiwan, Republic of China.
British Journal of Cancer (Impact Factor: 5.08). 11/2002; 87(9):966-70. DOI: 10.1038/sj.bjc.6600584
Source: PubMed

ABSTRACT Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB1-albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case-control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB1-albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4-5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0-2.1). In addition, the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection.

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    ABSTRACT: 4.1. Biomarkers for intake of heterocyclic aromatic amines 4.2. Polycyclic aromatic hydrocarbons in food 4.3. Biomarkers of N-nitroso compounds 4.4. Acrylamide 4.5. Alcohol biomarkers 4.6. Aflatoxins and other mycotoxins The mutagenic and carcinogenic heterocyclic aromatic amines are formed from precur-sors in meat and fish at temperatures exceeding 130°C and bind covalently to DNA after metabolic activation. Heterocyclic aromatic amines in urine have short half-lives but could be used to validate intake as estimated by questionnaires. Blood protein adducts and DNA adducts from various tissues have also been analysed. No epidemiological studies have yet been conducted in humans that have examined the association between heterocyclic aromatic amine exposure assessed by means of any biomarker and the risk of cancer. Polycyclic aromatic hydrocarbons, formed by the incomplete combustion of organic matter, are ubiquitous contaminants of the environment. There have been two main approaches to measurement of polycyclic aromatic hydrocarbons in complex matrices such as food: determination of around 15–20 polycyclic aromatic hydrocarbons, including carcinogenic compounds, or measurement of benzo[a]pyrene as a surrogate for all polycyclic aromatic hydrocarbons. The first approach gives a truer picture of the overall burden of these compounds in food; however, benzo[a]pyrene, because of its carcinogenic potency in experimental animals, represents a biologically significant measure. Most types of food contain measurable levels of polycyclic aromatic hydrocarbons and dietary exposure can be a significant effect in studies designed to determine occupational exposure or exposure due to urban pollution. N-nitroso compounds, and especially alkyl nitrosamines, are well known experimental carcinogens. Nitrosamines are present in significant quantities in tobacco smoke, while dimethylnitrosamine is also found in nitrate- or nitrite-treated foods. N-nitroso com-pounds can be formed endogenously at significant levels. Most epidemiological studies attempting to associate exposure to N-nitroso compounds and various human cancers have been inconclusive. The main problem was the inadequacy of methods for estimation not only of external exposure but, more importantly, of endo-genous exposure to N-nitroso compounds. Large-scale molecular epidemiological studies to determine the carcinogenic risk associated with the widespread presence in human DNA of O6-methylguanine, which plays an important role in mutagenesis, carcinogenesis and cytotoxicity by methylating agents, are lacking due to the lack of high throughput, high sensitivity assays for this adduct. The quantitatively most important DNA alkylation lesion N-7-methylguanine is not directly premutagenic, but can undergo spontaneous depurination to form mutagenic apurinic sites. N-7-Methylguanine accumulates more in tissues from smokers than nonsmokers, indicating that this biomarker could be used as an internal dosimeter for exposure to nitrosamines. Extensive research on tobacco-specific nitrosamines has failed to provide conclusive evidence of their role in human cancer, despite their being potent rodent carcinogens. The urinary 4-nitrosomethylamino)-1-(3-pyridyl)-1-butanone metabolites 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanol and its glucuronide are absolutely specific for tobacco exposure. Significant amounts of acrylamide can occur in certain food items high in carbohydrates and amino acids after heating. Acrylamide has been classified by IARC as “probably carcinogenic to humans” and the EU has classified it as a “Category 2 carcinogen and cate-gory 2 mutagen”. The adduct of acrylamide itself to the N-terminal valine in haemoglobin and to some extent the corresponding adduct of glycidamide have been applied in human studies to assess exposure. Epidemiological investigations have not shown an increased risk from dietary exposure but larger studies of populations with more varied diets are needed; in addition data from intervention studies and on urinary metabolites and cytogenetic effects would be useful Biomarkers of alcohol may potentially be used to address the limitations of questionnaires and interviews in exposure assessment in epidemiological studies of alcohol as a risk factor for cancer. The available biomarkers differ in sensitivity, specificity, ease of assay, and the time period that they reflect and none alone is ideal; combinations of various markers may allow for finer assessment of alcohol exposures in the future. Mycotoxins are ubiquitous toxic secondary metabolites of a number of species of moulds, and occur in foods and animal feeds. Naturally occurring aflatoxins are a cause of hepato-cellular carcinoma. Most European countries have imposed limits for aflatoxin B1 in foods and for aflatoxin M1 in milk. Urinary aflatoxin B1-N-7-guanine is an excellent biomarker for studies of acute exposure but does not reflect chronic intake of aflatoxin. Aflatoxin B1-albumin adducts are currently the most widely used biomarkers of aflatoxin in epidemiological studies. Assessment of functional polymorphisms in CYP3A4 and in other enzymes involved in the activation and detoxification of aflatoxin B1 may be used as markers of susceptibility to aflatoxins. The codon 249 mutation in p53 must be used cautiously as a marker of exposure to aflatoxin until evidence has been obtained from studies measuring both aflatoxin B1 adducts and mutations in the same individuals. ECNIS Network of Excellence
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    ABSTRACT: Chronic liver diseases are disastrous to health. Many factors are associated with their prevalence, hence endemicity. These are mainly infectious, parasitic and toxic. A survey was conducted in a village south to Cairo. Large industries concerned with iron and steel industry, metals smelting, cement manufacturing and electric station were located north to the village. A systematic random sample of houses was selected. All individuals inside the houses were invited to share in the study. Sample size was 84 individuals. Hepatitis markers were done (HBsAg and anti-HCV antibodies). The levels of some heavy metals were assessed; which were lead, mercury, arsenic, aluminum, manganese, nickel, chromium and cadmium. Levels of some trace elements were assessed. These were copper, iron, selenium and zinc. Aflatoxin B1 was assessed in serum. Assessment of schistosomal circulating antigen and antibodies was carried out. Abdominal ultrasonograghy was done to assess liver condition. Univariate logistic regression analysis was done to assess the association between studied variables and HBsAg or anti-HCV sero-positive subjects. The association between studied variables and bilharzial or fatty liver, diagnosed by ultrasonography, were also assessed. The univariate logistic regression analysis revealed odds ratios at the following results. For HBsAg seropositive subjects, aflatoxin B1, lead, chromium and schistosomal antigen and antibodies were higher than negative ones where odds ratios were; 6.2, 1.6, 1.6, 1.6 and 1.7, respectively. None of the variables showed statistically significant difference. For anti-HCV antibodies sero-positive subjects, aflatoxin B1 and chromium had the highest odds ratios among the studied variables, (odds ratios were 2.5 and 2.4, respectively). Bilharzial liver showed higher significant positivity of anti-HCV antibodies and insignificant decreased level of zinc than negative ones (odds ratios were 7.2 and 4.5, respectively). Fatty liver cases showed higher statistically significant positivity of anti-HCV antibodies and chromium than negative ones. Odds ratios were 8.0 and 7.1, respectively. Statistically significant lower level of aflatoxin B1 was shown in fatty liver than normal liver subjects. Multivariate logistic regression analysis for fatty liver showed that only anti-HCV antibodies sero-positivity had statistically significant odds ratio in comparison to chromium level and aflatoxin B1. It is concluded that some heavy metals, and Aflatoxin B1 had a definite association with liver diseases in the area under study. Having anti-HCV antibodies had a relation with fatty liver and with bilharzial liver more than having HBsAg. It is recommended that environmental management to factories nearby the village is urgently needed to decrease exposure to heavy metals. Prevention of hepatitis infection and aflatoxin exposure through different means is also recommended, other wise health care authorities would be confronted with unusual cases of HCC in the nearby future.
    The Journal of the Egyptian Public Health Association 02/2005; 80(3-4):355-88.
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    ABSTRACT: Aflatoxins are a group of mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus . They are potent inducers of hepatotoxicity. Those toxic compounds are ubiquitously found in food commodities such as nuts, cereals, spices and milks and dairy products. Aflatoxin B1 (AFB1) has been classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogen. Once AFB1 is ingested by humans, it is metabolized by liver enzymes into many metabolites. The study aimed to estimate the hepatotoxicity of AFB1 in workers occupationally exposed to wheat flour dust. Statistical analysis of the results revealed that Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), Alkaline phosphates (ALP) levels in the exposed workers were significantly higher compared to their controls. In the exposed workers, there were significant correlations between AFB1/Alb and the duration of exposure, and between the levels of AST and ALT and the level of AFB1/Alb. The present study concluded that the serum AFB1/Alb was significantly correlated with the duration of exposure in workers exposed to wheat flour dust, and this serum level has hepatotoxic effects in the exposed workers
    Egyptian Journal of Environmental Research. 01/2014; 2:51-56.

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