Use of human-derived liver cell lines for the detection of environmental and dietary genotoxicants; current state of knowledge.

Detoxification of patulin and ochratoxin A, two abundant mycotoxins, by lactic acid bacteria

Aromatic amines and heterocyclic aromatic amines (HAAs) are structurally related classes of carcinogens that are formed during the combustion of tobacco or during the high-temperature cooking of meats. Both classes of procarcinogens undergo metabolic activation by N-hydroxylation of the exocyclic amine group to produce a common proposed intermediate, the arylnitrenium ion, which is the critical metabolite implicated in toxicity and DNA damage. However, the biochemistry and chemical properties of these compounds are distinct, and different biomarkers of aromatic amines and HAAs have been developed for human biomonitoring studies. Hemoglobin adducts have been extensively used as biomarkers to monitor occupational and environmental exposures to a number of aromatic amines; however, HAAs do not form hemoglobin adducts at appreciable levels, and other biomarkers have been sought. A number of epidemiologic studies that have investigated dietary consumption of well-done meat in relation to various tumor sites re...

Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines.

Meat products are sources of protein with high biological value and an essential source of other nutrients, such as vitamins and minerals. Heating processes cause food to become more appetizing with changes in texture, appearance, flavor, and chemical properties by the altering of protein structure and other ingredients. During heat treatment, heterocyclic aromatic amines (HAAs), potent mutagens/carcinogens, are formed due to the Maillard reaction. The HAAs are classified in at least 2 groups: thermic HAAs (100 to 300 °C) and pyrolytic HAAs (>300 °C). This review focuses on the parameters and precursors which affect the formation of HAAs: preparation, such as the marinating of meat, and cooking methods, including temperature, duration, and heat transfer, as well as levels of precursors. Additionally, factors are described subject to pH, and the type of meat and ingredients, such as added antioxidants, types of carbohydrates and amino acids, ions, fat, and other substances inhibiting or enhancing the formation of HAAs. An overview of the different analytical methods available is shown to determine the HAAs, including their preparation to clean up the sample prior to extraction. Epidemiological results and human daily intake of HAAs obtained from questionnaires show a relationship between the preference for very well-done meat products with increased HAA levels and an enhanced risk of the incidence of cancer, besides other carcinogens in the diet. The metabolic pathway of HAAs is governed by the activity of several enzymes leading to the formation of DNA adducts or HAA excretion and genetic sensitivity of individuals to the impact of HAAs on human cancer risk.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1541-4337.12186

Heterocyclic Aromatic Amines in Cooked Meat Products: Causes, Formation, Occurrence, and Risk Assessment

This review compiles the contents of heterocyclic aromatic amines (HAAs) in foods and beverages, collected from literature data along the period from 1992 up to 2009. Also, it describes the factors that affect the formation of HAAs in foods, such as the cooking method, including temperature, time, and frequency of turning of meat, during cooking. Other factors depending on the type of food and the recipe followed are pH, amounts of HAA precursors, types of amino acids, presence of certain divalent ions, and content of substances with enhancing or inhibiting effects on the formation of HAAs. In addition, there are other factors, which depend on the type of food, such as muscle tissue and the presence of certain genes, since the RN− allele in pigs increases the glycogen content of muscle. The dispersion of the bibliographic data is evident, and there are scarce data, even no data, referred to individual HAAs. Considering that the diverging results can be due to several causes, possible recommendations are given in order to prevent the dispersion of the results and to achieve more valuable information, applied to determine the HAAs exposure. Although there are not direct indications that HAAs represent a serious health risk to the population, and common cancers are produced by many factors including xenobiotics, all measures to minimize the formation of HAAs should be foreseen, some of which are indicated.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1541-4337.2010.00141.x

Factors That Affect the Content of Heterocyclic Aromatic Amines in Foods

Exposure to beta-carbolines norharman and harman.

Investigation of the genotoxic effects of 2-amino-9H-pyrido[2,3-b]indole in different organs of rodents and in human derived cells.

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (AalphaC) are mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. MeAalphaC and AalphaC are activated to mutagenic metabolites by cytochrome P450-mediated N-oxidation to the corresponding N2-OH derivatives. The proximate mutagenic N2-OH derivatives of MeAalphaC and AalphaC did not react with deoxynucleosides or DNA. However, upon acetylation with acetic anhydride both reacted with 2'-deoxyguannosine and 3'-phospho-2'-deoxyguanosine, resulting in one adduct each, but not with other nucleosides or nucleotides. The adducts were identified as N2-(2'-deoxyguanosin-8-yl)-MeAalphaC, N2-(2'-deoxyguanosin-8-yl)-AalphaC, N2-(3'-phospho-2'-deoxyguanosin-8-yl)-MeAalphaC and N2-(3'-phospho-2'-deoxyguanosin-8-yl)-AalphaC by comparison with adducts of known structure obtained by reaction of the parent amines with acetylated guanine N3-oxide. N2-OH-MeAalphaC and N2-OH-AalphaC reacted with calf thymus DNA after addition of acetic anhydride. 32P-postlabelling analysis of modified DNA showed one major adduct co-migrating with N2-(3',5'-diphospho-2'-deoxyguanosin-8-yl)-MeAalphaC and N2-(3',5'-diphospho-2'-deoxyguanosin-8-yl)-AalphaC, respectively. Some minor adducts presumed to be undigested oligomers were also detected. 32P-postlabelling analysis of DNA from several organs of rats dosed orally with MeAalphaC showed that in vivo N2-(2'-deoxyguanosin-8-yl)-MeAalphaC also was the major adduct formed. Relative adduct level in DNA isolated from the liver of the rats was about 50.40 adducts/10(9) nt. The adduct levels were approximately 4-fold lower in the colon and the heart and approximately 12-fold lower in the kidney of the rats.

/pdf/syntheses-of-dna-adducts-of-two-heterocyclic-amines-2-amino-4vl76ouo5d.pdf

Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC) and 2-amino-9H-pyrido[2,3-b]indole (AαC) and identification of DNA adducts in organs from rats dosed with MeAαC

Heterocyclic aromatic amines--still a challenge for scientists.

During the frying of meat and fish, genotoxic heterocyclic amines (HCAs) are formed. The dietary exposure to HCAs may be implicated in the aetiology of human cancer, but there may be other factors in our diet that prevent the genotoxic effects of these compounds. Within the project described here, we plan to identify regional and individual cooking habits that affect HCA-levels in our food. These are determined with a validated analytical method and the exposure to HCAs is estimated by dietary assessment. Biomarker analysis will be employed to estimate recent or long-term exposure to HCAs. In order to identify genetically determined risk factors in humans, cell lines are genetically engineered expressing allelic variants of acetyl- and sulfotransferases implicated in HCA metabolism. Species differences of metabolism and toxicity of HCAs are assessed and the influence of the intestinal microflora on HCA-induced toxicity is evaluated. Dietary constituents that may reduce the genotoxicity of HCAs are screened for potential protective effects in in vitro and in vivo model systems. Finally, we will aim at human intervention studies to investigate if these protective factors are relevant for man. The objectives of this project are to estimate and possibly reduce the exposure levels to HCAs in Europe, to identify populations highly susceptible to HCA toxicity, and to reduce the toxic effects of HCAs by protective factors.

W. Pfau

Papers

Exposure to beta-carbolines norharman and harman.

Investigation of the genotoxic effects of 2-amino-9H-pyrido[2,3-b]indole in different organs of rodents and in human derived cells.

Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC) and 2-amino-9H-pyrido[2,3-b]indole (AαC) and identification of DNA adducts in organs from rats dosed with MeAαC

Heterocyclic aromatic amines--still a challenge for scientists.

Heterocyclic amines: human carcinogens in cooked food?