Carcinogenic Aromatic Amines Research Articles

Examination of primary aromatic amines content in polylactic acid straws and migration into food simulants using SERS with LC-MS

Polylactic acid (PLA) straws hold eco-friendly potential; however, residual diisocyanates used to enhance the mechanical strength can generate carcinogenic primary aromatic amines (PAAs), posing health risks. Herein, we present a rapid, comprehensive strategy to detecting PAAs in 18 brands of food-grade PLA straws and assessing their migration into diverse food simulants. Surface-enhanced Raman spectroscopy was conducted to rapidly screen straws for PAAs. Subsequently, qualitative determination of migrating PAAs into various food simulants (4 % acetic acid, 10 % ethanol, 50 % ethanol) occurred at 70 °C for 2 h using liquid chromatography-mass spectrometry. Three PAAs including 4,4′-methylenedianiline, 2,4′-methylenedianiline, and 2,4-diaminotoluene were detected in all straws. Specifically, 2,4-diaminotoluene in 50 % ethanol exceeded specific migration limit of 2 μg/kg, raising safety concerns. Notably, PAAs migration to 10 % and 50 % ethanol surpassed that to 4 % acetic acid within a short 2-hour period. Moreover, PLA straws underwent varying degrees of shape changes before and after migration. Straws with poly(butylene succinate) resisted deformation compared to those without, indicating enhanced heat resistance, while poly(butyleneadipate-co-terephthalate) improved hydrolysis resistance. Importantly, swelling study unveiled swelling effect wasn’t the primary factor contributing to the increased PAAs migration in ethanol food simulant, as there was no significant disparity in swelling degrees across different food simulants. FT-IR and DSC analysis revealed higher PAAs content in 50 % ethanol were due to highly concentrated polar ethanol disrupting hydrogen bonds and van der Waal forces holding PLA molecules together. Overall, minimizing contact between PLA straws and alcoholic foods is crucial to avoid potential safety risks posed by PAAs.

Uncovering the carcinogenicity of aromatic amines from food dyes and their link to oral cancer

Uncovering the carcinogenicity of aromatic amines from food dyes and their link to oral cancer

SERS Detection of Trace Carcinogenic Aromatic Amines Based on Amorphous MoO3 Monolayers.

Aromatic amines are important commercial chemicals, but their carcinogenicity poses a threat to humans and other organisms, making their rapid quantitative detection increasingly urgent. Here, amorphous MoO3 (a-MoO3) monolayers with localized surface plasmon resonance (LSPR) effect in the visible region are designed for the trace detection of carcinogenic aromatic amine molecules. The hot-electron fast decay component of a-MoO3 decreases from 301 fs to 150 fs after absorption with methyl orange (MO) molecules, indicating the plasmon-induced hot-electron transfer (PIHET) process from a-MoO3 to MO. Therefore, a-MoO3 monolayers present high SERS performance due to the synergistic effect of electromagnetic enhancement (EM) and PIHET, proposing the EM-PIHET synergistic mechanism in a-MoO3. In addition, a-MoO3 possesses higher electron delocalization and electronic state density than crystal MoO3 (c-MoO3), which is conducive to the PIHET. The limit of detection (LOD) for o-aminoazotoluene (o-AAT) is 10-9 M with good uniformity, acid resistance, and thermal stability. In this work, trace detection and identification of various carcinogenic aromatic amines based on a-MoO3 monolayers is realized, which is of great significance for reducing cancer infection rates.

SERS Detection of Trace Carcinogenic Aromatic Amines Based on Amorphous MoO3 Monolayers

AbstractAromatic amines are important commercial chemicals, but their carcinogenicity poses a threat to humans and other organisms, making their rapid quantitative detection increasingly urgent. Here, amorphous MoO3 (a‐MoO3) monolayers with localized surface plasmon resonance (LSPR) effect in the visible region are designed for the trace detection of carcinogenic aromatic amine molecules. The hot‐electron fast decay component of a‐MoO3 decreases from 301 fs to 150 fs after absorption with methyl orange (MO) molecules, indicating the plasmon‐induced hot‐electron transfer (PIHET) process from a‐MoO3 to MO. Therefore, a‐MoO3 monolayers present high SERS performance due to the synergistic effect of electromagnetic enhancement (EM) and PIHET, proposing the EM‐PIHET synergistic mechanism in a‐MoO3. In addition, a‐MoO3 possesses higher electron delocalization and electronic state density than crystal MoO3 (c‐MoO3), which is conducive to the PIHET. The limit of detection (LOD) for o‐aminoazotoluene (o‐AAT) is 10−9 M with good uniformity, acid resistance, and thermal stability. In this work, trace detection and identification of various carcinogenic aromatic amines based on a‐MoO3 monolayers is realized, which is of great significance for reducing cancer infection rates.

Omics-Based Approaches in Research on Textile Dye Microbial Decolorization.

The development of the textile industry has negative effects on the natural environment. Cotton cultivation, dyeing fabrics, washing, and finishing require a lot of water and energy and use many chemicals. One of the most dangerous pollutants generated by the textile industry is dyes. Most of them are characterized by a complex chemical structure and an unfavorable impact on the environment. Especially azo dyes, whose decomposition by bacteria may lead to the formation of carcinogenic aromatic amines and raise a lot of concern. Using the metabolic potential of microorganisms that biodegrade dyes seems to be a promising solution for their elimination from contaminated environments. The development of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has allowed for a comprehensive approach to the processes occurring in cells. Especially multi-omics, which combines data from different biomolecular levels, providing an integrative understanding of the whole biodegradation process. Thanks to this, it is possible to elucidate the molecular basis of the mechanisms of dye biodegradation and to develop effective methods of bioremediation of dye-contaminated environments.

Evaluation of polypropylene microporous membranes as extraction devices for determination of carcinogenic aromatic amines in smoker urine by GC–MS/MS

Exposure to tobacco smoke is highly correlated to the incidence of different types of cancer due to various carcinogenic compounds present in such smoke. Aromatic amines, such as 1-naphthylamine (1-NA) and 2-naphthylamine (2-NA), are produced in tobacco burning and are linked to bladder cancer. Miniaturized solid phase extraction techniques, such as microporous membrane solid phase extraction (MMSPE), have shown potential for the extraction of aromatic compounds. In this study, a bioanalytical method for the determination of 1-NA and 2-NA in human urine was developed using polypropylene microporous membranes as a sorptive phase for MMSPE. Urine samples were hydrolyzed with HCl for 1 h at 80 °C, after which pH was adjusted to 10. Ultrasound-assisted MMSPE procedure was optimized by factorial design as follows. To each sample, 750 µL of methanol was added, and ultrasound-assisted MMSPE was conducted for 1 h with four devices containing seven 2 mm polypropylene membrane segments. After extraction, the segments were transferred to 400 µL of hexane, and desorption was conducted for 30 min. Extracts were submitted to a simple and fast microwave-assisted derivatization procedure, by the addition of 10 µL of PFPA and heating at 480 W for 3 min, followed by clean-up with phosphate buffer pH 8.0 and GC–MS/MS analysis. Adequate linearity was obtained for both analytes in a range from 25 to 500 µg L−1, while the multiple reaction monitoring approach provided satisfactory selectivity and specificity. Intra-day (n = 6) and inter-day (n = 5) precision and accuracy were satisfactory, below 15 % and between 85 and 115 %, respectively. Recovery rates found were 91.9 and 58.4 % for 1-NA and 2-NA, respectively, with adequate precision. 1-NA was found in first-hand smokers’ urine samples in a concentration range from 20.98 to 89.09 µg in 24 h, while it could be detected in second-hand smoker's urine samples, and 2-NA detected in all first and second-hand smokers’ urine samples. The proposed method expands the applicability of low cost MMSPE devices to aromatic amines and biological fluids.

Screening of Azo-Dye-Degrading Bacteria from Textile Industry Wastewater-Activated Sludge

This study investigates the biodegradation of Reactive Red 141 (RR 141), an azo dye prevalent in the textile industry, by bacteria isolated from activated sludge in a textile effluent treatment plant. RR 141, characterized by nitrogen–nitrogen double bonds (-N=N-), contributes to environmental issues when improperly disposed of in textile effluents, leading to reduced oxygen levels in water bodies, diminished sunlight penetration, and the formation of potentially carcinogenic and mutagenic aromatic amines. This research focuses on identifying bacteria from activated sludge with the potential to decolorize RR 141. Microbiological identification employs MALDI-TOF-MS, known for its precision and rapid identification of environmental bacteria, enhancing treatment efficiency. Results highlight Bacillus thuringiensis and Kosakonia radicincitans as the most promising strains for RR 141 decolorization. Analysis of micro-organisms in activated sludge and database exploration suggests a correlation between these strains and the decolorization process. It is worth noting that this is the first report on the potential use of K. radicincitans for azo dye decolorization. Three distinct culture media—BHI, MSG, and MS—were assessed to investigate their impact on RR 141 decolorization. Notably, BHI and MSG media, incorporating a carbon source, facilitated the bacterial growth of both tested species (B. thuringiensis and K. radicincitans), a phenomenon absent in the MS medium. This observation suggests that the bacteria exhibit limited capability to utilize RR 141 dye as a carbon source, pointing towards the influence of the culture medium on the discoloration process. The study evaluates performance kinetics, decolorization capacity through UV-VIS spectrophotometry, potential degradation pathways via HPLC-MS analysis, phytotoxicity, and enzymatic activity identification. B. thuringiensis and K. radicincitans exhibit potential in decolorizing RR141, with 38% and 26% removal individually in 120 h. As a consortium, they achieved 36% removal in 12 h, primarily through biosorption rather than biodegradation, as indicated by HPLC-MS analyses. In conclusion, the research emphasizes the importance of exploring bacteria from activated sludge to optimize azo dye degradation in textile effluents. B. thuringiensis and K. radicincitans emerge as promising candidates for bioremediation, and the application of MALDI-TOF-MS proves invaluable for rapid and precise bacteria identification.

Carboxyl-functionalized covalent organic frameworks for the efficient adsorption of foodborne heterocyclic aromatic amines

The development of sorbents with high sensitivity and specificity for the effective extraction and assessment of carcinogenic heterocyclic aromatic amines (HAAs) in thermally processed foods is of utmost significance for food safety monitoring. Herein, we report the design and synthesis of a carboxyl-functionalized covalent organic framework (COF), TpPa-(COOH)2, through the regulation of carboxyl modification and crystallinity. The resulting flower-like TpPa-(COOH)2 exhibited excellent crystallinity and microporosity in an eclipsed stacking structure. Compared to TpPa, the introduction of carboxyl moieties in TpPa-(COOH)2 provided additional binding sites and significantly enhanced adsorption affinity for the 16 target analytes, despite having a smaller BET surface area. The adsorption of HAAs by TpPa-(COOH)2 followed the pseudo-second-order model and exhibited rapid kinetics (10–30 min). The experimental data demonstrated a strong fit with the Freundlich isotherm model, resulting in a maximum adsorption capacity of HAAs ranging from 1.8 to 155.8 mg/g. Additionally, the presence of interfering compounds only caused a slight reduction in both the equilibrium adsorption capacity and HAAs recovery. Notably, TpPa-(COOH)2 maintained its effective adsorption performance even after three adsorption–desorption cycles. Theoretical calculations indicated that the rapid binding of HAAs to TpPa-(COOH)2 could be attributed to the joint effects of electrostatic interaction, π–π interaction, C–H–π interaction, lone pair–π interaction, and hydrogen bonding. This adsorbent exhibits a notable enhancement in both adsorption capacity and mass transfer rates for the adsorption of HAAs, surpassing the performance of the reported adsorbents. This highlights its substantial potential for the precise detection of HAAs within food systems.

Facile preparation of sulfonated covalent triazine frameworks for effectively detection of six carcinogenic aromatic amines in cigarette smoke

FDA reported a HPHCs (Harmful and Potentially Harmful Constituents) list for tobacco products and tobacco smoke in 2012, which contained six carcinogenic aromatic amines (AAs). In this work, a sulfonated covalent triazine frameworks (CTF-SO3H) material was synthesized and used as a solid phase extraction (SPE) absorbent for highly effective enrichment and determination of six carcinogenic AAs in cigarette mainstream smoke (MSS), coupled with HPLC-MS/MS technique. The CTF-SO3H material was prepared with a rapid and facile method, which was superior to the general methods. The characterization with Nitrogen adsorption and desorption isotherm experiment, High resolution transmission electron microscopy (HTEM), etc, indicated that the CTF-SO3H material possessed sulfonic acid groups and abundant microporous structure. And the CTF-SO3H material showed good enrichment effect for AAs due to the synergistic effect of π-π stacking and electrostatic interactions. Limits of detection (LODs) of 6 AAs with the developed method were in the range of 0.01–0.11 ng cig−1. Recoveries of 6 AAs were between 80.40% and 106.00%, while the intra-day and inter-day precisions were good (i.e. RSDintra ≤ 6.40%, RSDinter ≤ 9.90%). Commercial cigarette MSS samples were analyzed with the developed method, and a commercial cation exchange SPE column was chosen for comparison. Results obtained by two methods showed a good consistency. However, the CTF-SO3H material needed less dosage, even could be reused for 4 times. Thus, the developed method not only showed high enrichment efficiency, but also was economical.

Comparison of aerobic and anoxic-oxic sequential batch reactors for treating textile wastewater

ABSTRACT The discharge of untreated textile dyeing wastewater containing azo dyes has significant ecological consequences. The incomplete biodegradation of these dyes can produce harmful and carcinogenic aromatic amines (AAs), which pose a threat to the environment. This study evaluates the treatment of real textile dyeing wastewater containing azo dyes by two different systems: an anoxic sequential batch reactor (A/O-SBR) and an aerobic sequential batch reactor (A-SBR). The effects of hydraulic retention time (HRT) on both systems were investigated in terms of chemical oxygen demand (COD), total nitrogen (TN), color, and AAs removal. Ranging between 85% and 92%, the COD removal efficiency was almost similar in the A/O-SBR and A-SBR systems, suggesting that the aerobic phase is primarily responsible for COD removal. However, A/O-SBR showed higher removal of color (90%) than A-SBR (75%) due to the presence of an anoxic phase. HRT has a significant impact on color removal in both systems. However, there was no significant effect on COD removal when HRT exceeded 12 h. According to LC-MS/MS analysis, increasing the HRT from 12 h to 24 h increased the AAs concentration in the anoxic phase, from 253 ng/L to 261 ng/L and slightly decreased the AAs concentration in the aerobic phase from 107 ng/L to 102 ng/L. This resulted in an overall improvement in both dye and AAs removal. The presence of aerobic phase in A/O-SBR and A-SBR demonstrates strong AAs removal capacity. GC-MS/MS analysis indicated that as the HRT of A/O-SBR and A-SBR increased, the number of by-products increased.

High-Field Asymmetric Waveform Ion Mobility Spectrometry Analysis of Carcinogenic Aromatic Amines in Tobacco Smoke with an Orbitrap Tribrid Mass Spectrometer.

Smoking is a risk factor for bladder cancer (BC), although the specific chemicals responsible for BC remain uncertain. Considerable research has focused on aromatic amines (AAs), including o-toluidine (o-tol), o-anisidine (o-anis), 2-naphthylamine (2-NA), and 4-aminobiphenyl (4-ABP), which are linked to human BC based on elevated BC incidence in occupationally exposed factory workers. These AAs arise at nanogram levels per combusted cigarette. The unambiguous identification of AAs, particularly low-molecular-weight monocyclic AAs in tobacco smoke extracts, by liquid chromatography-mass spectrometry (LC-MS) is challenging due to their poor performance on reversed-phase columns and co-elution with isobaric interferences from the complex tobacco smoke matrix. We employed a tandem liquid-liquid and solid-phase extraction method to isolate AAs from the basic fraction of tobacco smoke condensate (TSC) and utilized high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to high-resolution accurate mass (HRAM) Orbitrap LC-MS2 to assay AAs in TSC. The employment of FAIMS greatly reduced sample complexity by removing precursor co-isolation interfering species at the MS1 scan stage, resulting in dramatically improved signal-to-noise of the precursor ions and cleaner, high-quality MS2 spectra for unambiguous identification and quantification of AAs in TSC. We demonstrate the power of LC/FAIMS/MS2 by characterizing and quantifying two low-molecular-weight carcinogenic AAs, o-tol and o-anis, in TSC, using stable isotopically labeled internal standards. These results demonstrate the power of FAIMS in trace-level analyses of AA carcinogens in the complex tobacco smoke matrix.

The influence of heat treatment type on the fat component and heterocyclic aromatic amines formation in minced poultry meat products

In this study the influence of heat treatment type on the change in the fatty acid composition, indices and parameters of fat oxidation, the level of heterocyclic amines formation in the chopped poultry ready-to-eat products enriched with ω‑3 fatty acids and an antioxidant complex were studied. The composition of ingredients and recipes of ready-to-eat products are developed with consideration of the medical and biological requirements for the diets of oncological patients. These ready-to-eat products feature some antioxidant substances in their composition that can bind free radicals, and provide for a reduction in the risk of carcinogens formation during the manufacturing process. The heat treatment was run in several ways, also called as modes — cooking in a microwave oven (MW), cooking in a convection oven in the “convection” mode with preliminary short-term roasting, steam cooking. For comparison, the conventional, i. e. not enriched food sample was used as a control one. The introduction of ω‑3 fatty acids into the food formulation made it possible to change the fatty acid composition towards increasing the proportion of polyunsaturated fatty acids (PUFAs). It was found that the profile of fatty acids was influenced by both the ingredients of the product and the type of its heat treatment. The joint use of a PUFA source and a complex of antioxidants made it possible to obtain a ready-to-eat product with a high level of ω‑3; and to ensure the ratio of ω‑6 group acids: ω‑3 ratio amounts to 1–2:1. Heat treatment of enriched semi-finished products by microwave cooking and by steam cooking showed a lesser effect on the change in the content and composition of polyunsaturated fatty acids — the loss of fatty acids was 1.2% and 2.8%, respectively, while in the “convection” cooking mode with preliminary roasting this loss was equal to 3.5%. It was found that the antioxidant complex in the composition of the food product and gentle heat treatment methods cause less lipid peroxidation and the formation of carcinogenic heterocyclic aromatic amines (HAA) during the food manufacturing process.

Urine pH and Risk of Bladder Cancer in Northern New England.

Acidic urine pH is associated with rapid hydrolysis of N-glucuronide conjugates of aromatic amines into metabolites that may undergo metabolism in the bladder lumen to form mutagenic DNA adducts. We previously reported that consistently acidic urine was associated with increased bladder cancer risk in a hospital-based case-control study in Spain. Here, we conducted a separate study in northern New England to replicate these findings. In a large, population-based case-control study conducted in Maine, New Hampshire, and Vermont, we examined bladder cancer risk in relation to consistent urine pH, measured twice daily by participants over 4 consecutive days using dipsticks. In parallel, we collected spot urine samples and conducted laboratory measurements of urinary acidity using a pH meter. Unconditional logistic regression was used to estimate associations, adjusting for age, gender, race, Hispanic status, and state. Analyses were further stratified by smoking status. Among 616 urothelial carcinoma cases and 897 controls, urine pH consistently ≤ 6.0 was associated with increased bladder cancer risk (OR = 1.27; 95% confidence interval, 1.02-1.57), with the effect limited to ever-smokers. These findings were supported by analyses of a spot urine, with statistically significant exposure-response relationships for bladder cancer risk overall (Ptrend = 5.1×10-3) and among ever-smokers (Ptrend = 1.2×10-3). Consistent with a previous study in Spain, our findings suggest that acidic urine pH is associated with increased bladder cancer risk. Our findings align with experimental results showing that acidic urine pH, which is partly modifiable by lifestyle factors, is linked to hydrolysis of acid-labile conjugates of carcinogenic aromatic amines.

Carbonyl-trapping by phenolics and the inhibition of the formation of carcinogenic heterocyclic aromatic amines with the structure of aminoimidazoazaarene in beef patties

Carcinogenic heterocyclic aromatic amines (HAAs) with the structure of aminoimidazoazaarene (PhIP, MeIQx, IQ, and MeIQ) are produced by reaction of creatin(in)e, ammonia, and reactive carbonyls (phenylacetaldehyde, acrolein, and crotonaldehyde). In an attempt to provide efficient methodologies for HAA reduction in beef patties, this study: identified phloroglucinol as the most efficient phenolic to reduce HAA formation (76–96% inhibition); isolated and characterized by NMR and MS phloroglucinol/phenylcetaldehyde and phloroglucinol/acrolein adducts; and determined by LC-MS/MS adduct formation in beef patties treated with phloroglucinol. Obtained results suggested that addition of trihydroxyphenols (including phloroglucinol) to beef patties should decrease HAA formation. This was confirmed by both immersing beef patties in apple (or pear) juice before cooking (>90% inhibition) and including wheat bran in patty recipe. All these results confirm the key role of reactive carbonyls in the formation of carcinogenic HAAs and propose carbonyl-trapping as a way for controlling HAA formation in food products.

The Flexibility of β-Content, γ-Confidence Tolerance Intervals to Qualimetry a Simultaneous 22 Aromatic Amines Derived from Azo Dyes in Fabric Using a Sensitive GC-MS Technique.

Azo dyes are among the most widely used dyes in the textile industry, releasing a series of carcinogenic aromatic amines that can be absorbed through the skin. This work aims to show that 22 azo dye amines in a textile matrix can be quantified using a GC-MS method. Based on the notion of total error and β-content, γ-confidence tolerance intervals (β,γ-CCTI), a chemometric approach known as the "uncertainty profile" has been used to completely validate a GC-MS method for the simultaneous assay of 22 azo amines in fabrics. According to International Organization for Standardization (ISO) in ISO 17025 guidelines, analytical validation and measurement uncertainty estimates have evolved to be two main principles for ensuring the accuracy of analytical results and controlling the risk associated with their use. The calculated tolerance intervals allowed for the determination of the uncertainty limits at each concentration level. These limits when compared to the acceptable limits show that a significant portion of the expected outcomes is in conformity. Additionally, the relative expanded uncertainty values, calculated with a proportion of 66.7% and a 10% risk, do not exceed 27.7, 12.2, and 10.9% for concentration levels 1, 15, and 30 mg/L, respectively. The capability and flexibility of the β-content, γ-confidence intervals have been established through the use of this innovative approach to carrying out qualimetry of the GC-MS method depending on the behavior, required conformity proportion, and acceptable tolerance limits of each amine. An efficient GC-MS technique for the simultaneous determination of 22 azo amines in a textile matrix has been developed. Analytical validation using a new strategy based on the uncertainty concept is reported, uncertainty associated to measurement results is estimated, and the applicability of our approach to the GC-MS method is investigated.

Determination of 2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine (PhIP) and its precursors and possible intermediates in a chemical model system and roast pork

PhIP (2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine) is a carcinogenic heterocyclic aromatic amine often generated in thermal processing of food. Methods for PhIP and its precursors and possible intermediates determination in chemical model system and roast pork were established based on HPLC-Q-Orbitrap-HRMS and GC-MS. Results showed that the linearity of 8 targets was good in a certain concentration range (R2 ≥ 0.992). LODs and LOQs were in the range of 0.3–15 μg/kg and 1–50 μg/kg, respectively. Under the model system, the recoveries of 8 target compounds ranged from 86.3% to 119.2%, with relative standard deviations (RSDs) of 0.5–6.9%. The established method was applied to 8 targets determination in roast pork, with recoveries ranging from 87.1% to 107.3% and RSDs in the range of 1.2–7.8%. The developed methods are accurate and fast, which are suitable for PhIP and its precursors and possible intermediates analysis in chemical model system and actual meat products.

Advancing metabolic networks and mapping updated urinary metabolic fingerprints after exposure to typical carcinogenic heterocyclic aromatic amines

Heterocyclic aromatic amines (HAAs) were not only present in cooked foods and cigarette smoke, but also measured in airborne particles and diesel-exhaust particles. Typical HAAs have been reported to induce carcinogenicity and metabolic disturbances, but how these hazardous compounds interfere with metabolic networks by regulating metabolic pathways and fingerprinting signature metabolites as biomarkers remains ambiguous. We developed an advanced strategy that adopted chemical isotope labeling ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry for urinary nontargeted metabolomics analysis to gain new insight into in vivo physiological responses stimulated by exposure to typical HAAs. Rats were orally administered with a single dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (1 and 10 mg/kg bw) and their D3-isotopic compounds, respectively, and urine samples were then continuously collected within 36 h. Metabolomics data were acquired and processed by classical multivariate statistical analysis, while urinary metabolites were further identified and characterized according to mass spectrometric fragmentation rules, time- and dose-dependent profiles, and calibration of synthesized standards. We monitored 23 and 37 urinary metabolites as the biotransformation products of PhIP and MeIQx, respectively, and first identified demethylated metabolites of PhIP, tentatively named 2-amino-6-phenylimidazo[4,5-b]pyridine, and dihydroxylation products of classical HAAs as short-term biomarkers of exposure to further unravel the metabolic networks. In addition, our findings revealed that both HAAs significantly disturb histidine metabolism, arginine and proline metabolism, tryptophan metabolism, pyrimidine metabolism, tricarboxylic acid cycle, etc. Furthermore, we found that histamine, methionine, alanine, and 4-guanidinobutanoic acid could be considered potential characteristic biomarkers for the oncogenicity or carcinogenicity of both PhIP and MeIQx and screened their specific key pivotal metabolites. The current metabolomics approach is applicable in mapping updated urinary metabolic fingerprints and identifying potential specific biomarkers for HAAs-induced early tumorigenesis.

Occupation-related cancer in urology-Current knowledge including environmental medical aspects

Occupation-related cancers are of considerable importance, which is not yet adequately recognized in the field of urology. The three numerically most significant entities are tumors of the urinary tract caused by carcinogenic aromatic amines or polycyclic aromatic hydrocarbons, renal cell cancer after high exposure to the solvent trichloroethylene, and mesotheliomas of the tunica vaginalis of the testis after exposure to asbestos; however, these can only be recognized as occupation-related if an occupational history regarding the hazard relevant to the organ bearing the tumor is documented from the beginning of employment, e.g. by aquestionnaire. This is because the relevant exposures generally date back several decades. With the exception of high exposure to trichloroethylene, the substances mentioned can also environmentally trigger the same tumors. In the context of environmental risk factors, it is of considerable importance that smoking is now considered to be atrigger for some 50% of all bladder cancers in men and women; however, smoking cessation results in areduction in smoking-related cancer risk of over 30% after only 3-4years. Work and commuting accidents, which are considered occupational risks, can lead to urological sequelae. For example, increased tumors of the bladder can occur after spinal cord injury lasting longer than 10years.

Differences in β-naphthylamine metabolism and toxicity in Chinese hamster ovary cell lines transfected with human CYP1A2 and NAT2*4, NAT2*5B or NAT2*7B N-acetyltransferase 2 haplotypes.

β-naphthylamine (BNA) is an important aromatic amine carcinogen. Current exposures derive primarily from cigarette smoking including e-cigarettes. Occupational and environmental exposure to BNA is associated with urinary bladder cancer which is the fourth most frequent cancer in the United States. N-acetyltransferase 2 (NAT2) is an important metabolizing enzyme for aromatic amines. Previous studies investigated mutagenicity and genotoxicity of BNA in bacteria and in rabbit or rat hepatocytes. However, the effects of human NAT2 genetic polymorphism on N-acetylation and genotoxicity induced by BNA still need to be clarified. We used nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells that were stably transfected with human CYP1A2 and NAT2 alleles: NAT2*4 (reference allele), NAT2*5B (variant slow acetylator allele common in Europe) or NAT2*7B (variant slow acetylator allele common in Asia). BNA N-acetylation was measured both in vitro and in situ via high-performance liquid chromatography (HPLC). Hypoxanthine phosphoribosyl transferase (HPRT) mutations, double-strand DNA breaks, and reactive oxygen species (ROS) were measured as indices of toxicity. NAT2*4 cells showed significantly higher BNA N-acetylation rates followed by NAT2*7B and NAT2*5B. BNA caused concentration-dependent increases in DNA damage and ROS levels. NAT2*7B showed significantly higher levels of HPRT mutants, DNA damage and ROS than NAT2*5B (p < 0.001, p < 0.0001, p < 0.0001 respectively) although both are slow alleles. Our findings suggest that BNA N-acetylation and toxicity are modified by NAT2 polymorphism. Furthermore, they confirm heterogeneity among slow acetylator alleles for BNA metabolism and toxicity supporting differential risk for individuals carrying NAT2*7B allele.

Determination of Carcinogenic Primary Aromatic Amines Contained as Impurities in Synthetic Organic Colorants.

Several primary aromatic amines (PAAs) have been designated carcinogenic or suspected of carcinogenicity. Several kinds of PAAs may occur either via the reduction of azo compounds or as impurities in azo colorants or other agents. An analytical method was developed and applied to determine whether certain PAAs are present as impurities in synthetic organic colorants. Target chemicals were analyzed by the ultrasound extraction of the synthetic organic colorant with a hydrochloric acid solution containing 20% methanol, followed by conversion from an acidic to alkaline solution, and then extraction using a diatomaceous earth column. We analyzed certain PAAs in 38 synthetic organic colorants, resulting in the detection of 2,4-dimethylaniline in four samples at 1.2 to 19 μg/g, o-toluidine in three samples at 1.0 to 3.4 μg/g, p-phenylazoaniline in two samples at 74 to 305 μg/g, and, in one sample each, 2,4,5-trimethylaniline (13 μg/g), 5-nitro-o-toluidine (12 μg/g), and 2-methyl-4-(2-tolylazo)aniline (13 μg/g). Nearly all PAAs were determined to be starting materials for colorant synthesis, although p-phenylazoaniline in Yellow No. 407 was apparently a byproduct formed during synthesis. For Red No. 225, in which high concentrations of p-phenylazoaniline were detected, additional samples were purchased from five companies, and p-phenylazoaniline was detected at concentrations of 88 to 370 μg/g in all samples. A method to analyze certain PAAs contained as impurities in synthetic organic colorants was developed, and the actual status of them in colorants was clarified. The analytical method developed in this study for the determination of certain PAAs contained as impurities in synthetic organic colorants may be used to improve the safety of colorants.