Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Kyrtopoulos, Soterios A.
MetadataShow full item record
AbstractThe 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.
CitationIn: Biomarkers of carcinogen exposure and early effects. Ed. Peter B. Farmer, Jean M. Emeny. Lodz 2006, p. 83-136.
Description4.1. 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
Series/Report no.ECNIS Report
SponsorsECNIS Network of Excellence