Unveiling Condensed Aromatic Amines as Noteworthy Genotoxic Components in PM2.5 Dissolved Organic Matter.

Effect of charcoal types and grilling conditions on formation of heterocyclic aromatic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled muscle foods

Impact of seed-roasting treatment on polycyclic aromatic hydrocarbons, 3-MCPD esters, heterocyclic amines and volatile components formation in sunflower oil

Cytochrome P450 1A subfamily enzymes (CYP1As) are important molecules in the metabolic activation of carcinogens such as polycyclic aromatic hydrocarbons and heterocyclic amines and are induced by their substrate exposure. There are species, sex, and organ differences in the induction of CYP1As, and susceptibilities to carcinogens are closely related to the constitutive and carcinogen-induced levels of CYP1As in target organs of experimental rodents. In this study, we investigated the induction of CYP1As and their species or sex differences after treatment with various chemicals using experimental animals and cultured cell lines. We found that: 1) newly established reporter cell lines, HepG2-A10 and KanR2-XL8, can be used for determining of activation of the aryl hydrocarbon receptor (AhR), a key transcription factor in the expression of CYP1As; 2) monocyclic aromatic amine (2-methoxy-4-nitroaniline) induced hepatic CYP1As in rats but not in other rodents in an AhR-independent manner; 3) androgen suppressed the constitutive expression or heterocyclic aromatic amine (Trp-P-1)-dependent induction of these enzymes in pigs and mice; and 4) nicardipine, a dihydropyridine calcium channel blocker, increased hepatic CYP1A expression in rats and augmented 3-methylcholanthrene-mediated induction of CYP1As and DNA-adduct formation in HepG2 cells. These findings indicate that there are species or sex differences in the induction of hepatic CYP1As via AhR-independent and unexplained transcriptional mechanisms. The elucidation of these mechanisms will aid in finding new predictors or developing new prevention strategies for chemical-induced carcinogenesis.

ABSTRACTThis study investigated the simultaneous formation of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) in gas-grilled beef satay at different temperatures (150, 200, 250, 300, and 350°C). Solid-phase extraction (SPE) was used for sample clean-up. Fifteen PAHs were determined using high performance liquid chromatography with fluorescence detection (HPLC-FLD) and nine HCAs were quantified using liquid chromatography tandem-mass spectrometry (LC-MS/MS) with a gradient programme. The lowest significantly concentrations of PAHs and HCAs were generated at 150°C; the formation of PAHs and HCAs simultaneously increased with temperatures. Benzo[a]pyrene was detected in all samples and increased markedly at 300 and 350°C. The sums of 4 PAHs (PAH4) in marinated beef satay at 300 and 350°C exceeded the maximum level in Commission Regulation (EU) 2015/1125. Significant reductions of polar and non-polar HCAs (except PhIP) were found in marinated beef satay across all temperatures. Overall, PAHs and HCAs showed opposite trends of formation in beef satay with marination.

The effects of honey-spices marination on simultaneous formation of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) in gas-grilled beef satay were investigated at different grilling temperatures (150 °C, 250 °C, and 350 °C). Beef satay samples used in this study were prepared using two types of honey-spices marination (Apis mellifera-spices and Trigona sp.-spices). Quantifications of fifteen PAHs using high performance liquid chromatography with fluorescence detection (HPLC-FLD) and nine HCAs using liquid chromatography tandem-mass spectrometry (LC–MS/MS) were performed with gradient programme. Results on PAHs and HCAs in marinated samples were compared with control. Highest concentrations (p < 0.05) of PAHs (marinated beef satay) and HCAs (control) were detected at 350 °C. The most prominent PAH and HCA were phenanthrene (24.61–84.36 ng/g) and 9H-pyrido-[4,3-b]indole (Norharman) (2.67–393.89 ng/g). Marination significantly (p < 0.05) reduced naphthalene, fluorene, pyrene, 2-amino-9H-pyrido[2,3-b]indole (AαC), 1-methyl-9H-pyrido-[4,3-b]indole (Harman), and Norharman in gas-grilled beef satay across all temperatures. Overall, inverse quantitative profiles of PAHs and HCAs formation were observed in marinated gas-grilled beef satay.

Dietary exposure to potentially high‐risk compounds such as heterocyclic aromatic amines (HAAs) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), formed in meat during cooking, or from exposure to hemeiron naturally occurring in meat, have all been proposed as possible mechanisms responsible for the reported weak association between red and processed meat consumption and increased cancer risk in observational studies. In this study, a systematic review of the mechanistic literature was used to examine the available evidence‐base to determine if sufficient evidence exists to link heme iron, BaP, or HAAs from red and processed meat to increased cancer risk. Inclusion criteria required that study designs accommodate exposure from a whole food or in the context of a well‐described diet and that outcomes adequately represent normal physiology of the tissue of interest. Results regarding dietary Ba Prevealed, of 51 studies published since 2000, only 4 met the full criteria for inclusion. The primary reasons for study exclusion were a failure to evaluate effects of BaP administered orally or as part of a diet and a failure to adequately represent non‐cancerous tissue physiology. Regarding dietary HAAs, of 294studies published since 2000, 29 publications met the full criteria for inclusion. Only 3 of the included studies utilized an animal model to investigate HAA intake from foods or as part of a well‐described diet and only one type of HAA was evaluated in the included animal studies. In the human studies there was near‐exclusive use of a single, non‐comprehensive database, rather than actual and/or direct analytical measurement of dietary HAAs. And regarding dietary heme iron, of 210 search results since 2000, only 13publications met the full criteria for inclusion. The type of heme iron supplemented in animal diets, as surrogates for naturally occurring heme iron, were found to independently affect the outcomes in some studies. The use of hemeiron surrogates has not been systematically validated against naturally occurring heme iron. For all compounds, the exclusive use of carcinogen‐treated animals was questioned as well as the use of in vitro cytotoxicity assays as surrogates for normal colon physiology. In each case, evidence was found to be weak and inadequate in both humans and animals concerning the mechanistic relationship between the dietary exposures of BaP, HAAs, or heme iron and human cancer.Support or Funding InformationSupport from the Beef Checkoff

The effects of wheat fiber (1 and 2%) and the mixture of xanthan and guar gums (0.5%; 4:1) incorporations in beef patties on the levels of formed polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) were evaluated. In this regard, the samples were stored at − 18 °C during different storage times (days 0, 45, and 90) and then were grilled at 175 °C for 5 min. At day 0, a significant (P < 0.05) difference in the formation of PAHs and HCAs among treated beef patties and control samples was noted. The formation of carcinogenic compounds at day 0 was reduced while fiber and gums together were added. The highest reduction in PAHs and HCAs levels among treatments was related to benzo [b] fluorantene (36–42%) and 2-amino-3-methyl-imidazo [4, 5-f] quinoline (60–74%), respectively. Also, the frozen storage of samples for 45 and 90 days significantly (P < 0.05) caused an increase and decrease in the PAHs and in HCAs levels, respectively. Therefore, the incorporation the combination of wheat fiber (2%), xanthan and guar gums (0.5%) can be suggested as a promising strategy to reduce the levels of PAHs and HCAs in beef patties.

Chapter 25 Toxicological Aspects of Aromatic Heterocyclic Amines

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 reported a positive association between cancer risk and well-done meat consumption, although some studies have shown no associations between well-done meat and cancer risk. A major limiting factor in most epidemiological studies is the uncertainty in quantitative estimates of chronic exposure to HAAs, and thus, the association of HAAs formed in cooked meat and cancer risk has been difficult to establish. There is a critical need to establish long-term biomarkers of HAAs that can be implemented in molecular epidemioIogy studies. In this review, we highlight and contrast the biochemistry of several prototypical carcinogenic aromatic amines and HAAs to which humans are chronically exposed. The biochemical properties and the impact of polymorphisms of the major xenobiotic-metabolizing enzymes on the biological effects of these chemicals are examined. Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and emerging biomarkers of HAAs that may be implemented in molecular epidemiology studies are discussed.

Animal work implicates chemical carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) as contributing to the development of colorectal cancer (CRC). The epidemiologic evidence, however, remains inconsistent possibly due to intra-individual variation in bioactivation of these compounds. We conducted a case-control study of colorectal adenoma (914 cases, 1185 controls) and CRC (496 cases, 607 controls) among Japanese Americans, European Americans and Native Hawaiians to investigate the association of genetic variation in the PAH and HAA bioactivation pathway (CYP1A1, CYP1A2, CYP1B1, AHR and ARNT) identified through sequencing with risk of colorectal neoplasia, as well as their interactions with smoking and intakes of red meat and HAAs. The A allele for ARNT rs12410394 was significantly inversely associated with CRC [odds ratios (ORs) and 95% confidence intervals (CIs) for GG, AG and AA genotypes: 1.00, 0.66 (0.48-0.89), 0.54 (0.37-0.78), P(trend) = 0.0008] after multiple comparison adjustment. CYP1A2 rs11072508 was marginally significantly associated with CRC, where each copy of the T allele was associated with reduced risk (OR: 0.72, 95% CI: 0.58-0.88, P(trend) = 0.0017). No heterogeneity of genetic effects across racial/ethnic groups was detected. In addition, no significant interaction was observed after adjusting for multiple testing between genetic variants and pack-years of smoking, intake of red meat or HAAs (PhIP, MeIQx, Di-MeIQx or total HAAs) or NAT2 genotype (Rapid versus Slow or Intermediate). This study suggests that the genomic region around ARNT rs12410394 may harbor variants associated with CRC.

Formation mechanisms, detection methods and mitigation strategies of acrylamide, polycyclic aromatic hydrocarbons and heterocyclic amines in food products

The behavior of polycyclic aromatic hydrocarbons (PAHs) is affected by dissolved organic matter (DOM) present in pore water of soils and sediments. Since partitioning to DOM reduces the bioavailable or freely dissolved PAH concentration in pore water, it is important to assess the effect of environmental variables on the magnitude of dissolved organic matter to water partition coefficients (K (DOC)). The objective of this study was to apply passive samplers to measure freely dissolved PAHs allowing depletion from the aqueous phase. The method was applied to determine K (DOC) at different temperatures for a selection of PAHs with natural DOM of very different origin. Freely dissolved concentrations of (spiked) phenanthrene, anthracene, fluoranthene, pyrene, and benzo[e]pyrene were determined by exposing polydimethylsiloxane (PDMS) fibers to aqueous solutions containing DOM extracted from freshwater sediments from Finland and the Netherlands. The K (DOC) values were subsequently calculated at different temperatures (3.2, 20, and 36 degrees C) by including temperature-dependent PDMS to water partition coefficients (K (PDMS)) in a mass balance. Furthermore, the effect of temperature on partitioning of PAHs to PDMS fibers or DOM was assessed by comparing the enthalpy of sorption to the excess enthalpy of dissolution of liquid PAHs. Partitioning to DOM resulted in a decrease of freely dissolved concentrations with increasing DOM concentrations and a large range in log K (DOC) values at 20 degrees C for benzo[e]pyrene was observed (log K (DOC) = 4.93-6.60 L kg(-1) organic carbon). An increase of 10 degrees C in temperature resulted in a decrease of K (PDMS) by 0.09 to 0.13 log units for phenanthrene to pyrene and a decrease of K (DOC) by 0.13 log units for pyrene. The calculated enthalpies of sorption were less exothermic than the (negative) excess enthalpies of dissolution as expected for non-specific interactions between PAHs and PDMS or DOM. The bioavailability of PAHs in sedimentary pore waters can be accurately determined by application of PDMS fibers (without requiring negligible depletion) in the presence of natural DOM with different sorption affinity for PAHs. The observed natural variability in log K (DOC) values for different sediments shows that large differences can occur in freely dissolved PAH concentrations in pore water and properties of DOM should be taken into account in predicting the bioavailability of PAHs. Furthermore, the effect of temperature on the partitioning behavior of PAHs shows that interactions between PAHs and environmental sorbents are comparable to interactions between PAHs in their pure condensed liquid phase and calculated excess enthalpies can be safely used to directly correct partition coefficients for temperature. The application of PDMS fibers in measuring freely dissolved PAH concentrations can be used to study structural and thermodynamic aspects of PAH sorption to natural DOM as well as other environmental processes such as enhanced diffusion phenomena in pore water that are dependent on the amount (or concentration) of DOM, sorption affinity of DOM, and hydrophobicity of PAHs. These environmental factors will therefore give further insight into the site-specific exposure to freely dissolved PAH concentrations in soil and sedimentary pore water.

The impact of temperature-controlled smoldering smoking on polycyclic aromatic hydrocarbons and heterocyclic amines contents in Frankfurter-type sausages

How do we judge what causes cancer? the meat controversy.

Heterocyclic aromatic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) as carcinogenic chemical compounds can be formed during high-temperature heating of beef patties. The current study was aimed to evaluate the effects of nutmeg and ginger essential oils incorporated in two concentrations (0.02 and 0.04%) and their nanoemulsions on the HCAs and PAHs formation in grilled beef patties during production time, 45- and 90-days storage in a freezing condition at − 18 °C. According to results, the HCAs and PAHs levels in essential oil and nanoemulsion added grilled beef patties significantly decreased while compared to the control. The addition of 0.04% nutmeg oil nanoemulsion in grilled beef patties led to the highest reduction in 2-amino-3,4-dimethyl-imidazo[4,5-f] quinoline (100% reduction) and benzo [b] fluorantene (46% reduction). The storage time of beef patties significantly affected the concentration of HCAs and PAHs. In this context, with increase in storage time, the levels of HCAs and PAHs were decreased and increased, respectively. The formation of 2-amino-3,4-dimethyl-imidazo[4,5-f] quinoline in all grilled beef patties containing nutmeg oil and its nanoemulsion was reduced by 100% after 45 and 90 days storage. However, the lowest increase in the formation of PAHs was related to dibenzo [a,h] anthracene by 25% in grilled beef patties containing 0.04% nutmeg oil nanoemulsion at the end of storage time. Generally speaking, nutmeg oil and especially prepared nanoemulsion have a great impact in preventing of the carcinogens compound formation in grilled patties.