Is Ultra-High Temperature Processed Milk Safe in Terms of Heterocyclic Aromatic Amines?
Ontology highlight
ABSTRACT:
SUBMITTER: Oz F
PROVIDER: S-EPMC8227235 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also can undergo a co-oxidation reaction with oxy-hemolgobin (HbO2) to form methemoglobin (met-Hb) and the arylnitroso intermediates, which react with the ?-Cys(93) chain of Hb to form Hb-arylsulfinamide adducts. The biochemistry of arylamine metabolism has been exploited to biomonitor certain AAs through their Hb arylsulfinamide adducts in humans. We examined the reactivity of HbO2 with the N-hydroxylated metabolites of 4-aminobiphenyl (ABP, HONH-ABP), aniline (ANL, HONH-ANL), and the HAAs 2-amino-9H-pyrido[2,3-b]indole (A?C, HONH-A?C), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, HONH-PhIP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx, HONH-MeIQx). HONH-ABP, HO-ANL, and HONH-A?C induced methemoglobinemia and formed Hb sulfinamide adducts. However, HONH-MeIQx and HONH-PhIP did not react with the oxy-heme complex, and met-Hb formation and chemical modification of the ?-Cys(93) residue were negligible. Molecular modeling studies showed that the distances between the H-ON-AA or H-ON-HAA substrates and the oxy-heme complex of HbO2 were too far away to induce methemoglobinemia. Different conformational changes in flexible helical and loop regions around the heme pocket induced by the H-ON-AA or H-ON-HAAs may explain the different proclivities of these chemicals to induce methemoglobinemia. Hb-Cys(93?) sulfinamide and sulfonamide adducts of ABP, ANL, and A?C were identified, by Orbitrap MS, following the proteolysis of Hb with trypsin, Glu-C, or Lys-C. Hb sulfinamide and sulfonamide adducts of ABP were identified in the blood of mice exposed to ABP, by Orbitrap MS. This is the first report of the identification of intact Hb sulfinamide adducts of carcinogenic AAs in vivo. The high reactivity of HONH-A?C with HbO2 suggests that the Hb sulfinamide adduct of A?C may be a promising biomarker of exposure to this HAA in humans.
| S-EPMC4801648 | biostudies-literature
Project description:2-Amino-9H-pyrido[2,3-b]indole (A?C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. UDP-glucuronosyltransferases (UGT) detoxicate many procarcinogens and their metabolites. The genotoxic N-hydroxylated metabolite of A?C, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-A?C), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(?-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (A?C-HON(2)-Gluc) and O-(?-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (A?C-HN(2)-O-Gluc). A?C-HON(2)-Gluc is a stable metabolite but A?C-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-A?C. We measured the rates of formation of A?C-HON(2)-Gluc and A?C-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. A?C-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. In contrast, A?C-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-A?C. UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. However, we found that the N3-Gluc of HONH-PhIP also covalently bound to DNA at higher levels than HONH-PhIP. The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH-A?C and HONH-PhIP as opposed to their detoxicated N(2)-Gluc isomers. The regioselective O-glucuronidation of HONH-A?C and HONH-PhIP, by UGT1A9, is a mechanism of bioactivation of these ubiquitous HAAs.
| S-EPMC4868641 | biostudies-literature
Project description:Heterocyclic aromatic amines (HAA) are formed in cooked meat, poultry and fish but also arise in tobacco smoke and exhaust gases. HAA are potential human carcinogens, which require metabolic activation to exert their genotoxicity. Human tissues can bioactivate HAA to produce reactive intermediates that bind to DNA. HAA DNA adduct formation occurs in human hepatocytes; however, the potential of HAA to form DNA adducts has not been investigated in human T lymphocytes. In this study, we investigated the ability of human T lymphocytes activated with PMA/Ionomycin or CD3/CD28 to express functional CYP1 activity and bioactivate three major HAA: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-9H-pyrido[2,3-b]indole (A?C) to form DNA adducts. Adducts were measured by ultraperformance liquid chromatography-electrospray ionization/multistage scan mass spectrometry. The highest level of DNA adducts occurred for A?C (16 adducts per 109 nucleotides), followed by PhIP (9 adducts per 109 nucleotides). In contrast, DNA adducts formed from MeIQx and the structurally related aromatic amine 4-aminobiphenyl, a known human carcinogen, were below the limit of detection (< 3 adducts per 109 nucleotides). Moreover, we demonstrate that A?C is a potent inducer of CYP1A1 and CYP1B1 activity through a transcriptional mechanism involving the AhR pathway. Overall, our results highlight the capacity of activated human T lymphocytes to more efficiently bioactivate A?C to form DNA adducts than other prominent HAA or 4-ABP. Environ. Mol. Mutagen. 57:656-667, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC5123841 | biostudies-literature
Project description:A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in the hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AalphaC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at a level just above the LOQ (65 pg/g hair), indicating that PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6 month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0 and 0.080 to 800 microg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AalphaC and MeIQx were detected in fur at dosages > or =0.8 mug AalphaC/kg body weight and > or =8 microg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p values < 0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising tissue with by which we can noninvasively biomonitor the chronic exposure to PhIP, a potential human carcinogen.
| S-EPMC2787961 | biostudies-literature
Project description:Here, we report the draft genome sequences of 3 Bacillus sporothermodurans strains isolated from ultra-high-temperature milk products in South Africa and Brazil and the type strain MB 581 (DSM 10599). The genomes will provide valuable information on the molecular dynamics of heat resistance in Bsporothermodurans.
| S-EPMC6544184 | biostudies-literature
Project description:DNA adduct formation of the aromatic amine, 4-aminobiphenyl (4-ABP), a known human carcinogen present in tobacco smoke, and the heterocyclic aromatic amines (HAAs), 2-amino-9H-pyrido[2,3-b]indole (A?C), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx), potential human carcinogens, which are also present in tobacco smoke or formed during the high-temperature cooking of meats, was investigated in freshly cultured human hepatocytes. The carcinogens (10 ?M) were incubated with hepatocytes derived from eight different donors for time periods up to 24 h. The DNA adducts were quantified by liquid chromatography-electrospray ionization mass spectrometry with a linear quadrupole ion trap mass spectrometer. The principal DNA adducts formed for all of the carcinogens were N-(deoxyguanosin-8-yl) (dG-C8) adducts. The levels of adducts ranged from 3.4 to 140 adducts per 10(7) DNA bases. The highest level of adduct formation occurred with A?C, followed by 4-ABP, then by PhIP, MeIQx, and IQ. Human hepatocytes formed dG-C8-HAA-adducts at levels that were up to 100-fold greater than the amounts of adducts produced in rat hepatocytes. In contrast to HAA adducts, the levels of dG-C8-4-ABP adduct formation were similar in human and rat hepatocytes. These DNA binding data demonstrate that the rat, an animal model that is used for carcinogenesis bioassays, significantly underestimates the potential hepatic genotoxicity of HAAs in humans. The high level of DNA adducts formed by A?C, a carcinogen produced in tobacco smoke at levels that are up to 100-fold higher than the amounts of 4-ABP, is noteworthy. The possible causal role of A?C in tobacco-associated cancers warrants investigation.
| S-EPMC3118939 | biostudies-literature
Project description:The impact of black cumin usage on some qualitative properties and formation of heterocyclic aromatic amines (HAAs) in meatball production was investigated. It was found that black cumin usage rate, cooking process and temperature had a significant effect (p<0,01) on the water content, pH, and thiobarbituric acid reactive substances (TBARS) values of meatballs. On the other hand, black cumin usage significantly (p<0,01) reduced the water content and cooking loss. The water content and cooking loss of the meatballs decreased with increases in the usage rate. While IQx, IQ, MeIQ, 7,8-DiMeIQx, 4,8-DiMeIQx, A?C, and MeA?C could not be detected in meatballs, varying amounts of MeIQx (up to 1,53 ng/g) and PhIP (up to 1,22 ng/g) were determined. The total amounts of HAAs ranged between non-detected (nd) to 2,75 ng/g. Both the usage rate and cooking temperature had a very significant effect (p<0,01) on the total contents of HAAs. The total amounts of HAAs were decreased in correlation with the increases in the usage rate; the proportion which is increased when the cooking temperature increased as well. Results of the present study suggested that addition of black cumin may have a substantial role in decreasing the TBARS value, cooking loss, and HAA contents during meatball production. Therefore, using of black cumin in meatball production has been suggested.
| S-EPMC6711510 | biostudies-literature
Project description:The nutritional status of meat is tarnished by its association with the induced cooking contaminants. The aim of this study was to assess the heterocyclic aromatic amines profile and contents in processed chicken in Burkina Faso. Eight polar and apolar heterocyclic aromatic amines (HAAs) including 2-mino-3-methylimidazo[4,5-f]quinolone (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P2), 2-mino-9H-pyrido-[2,3-b]indole (AαC), 2-amino-1-methyl-6-phenylimidazo[4, 5- ]pyridine (PhIP), 2-amino-3-methyl-9H-pyrido[2,3-b] indole (MeAαC), 2-amino-3,4,8-rimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,8-imethylimidazo[4,5-]quinoxaline (MeIQx) were screened by high performance liquid chromatography from 29 samples of flamed chicken and 66 samples of braised chicken collected in Ouagadougou city. Apolar HAAs and polar HAAs were respectively 12 and 3 times more abundant in flamed chickens (32.66±10 and 3.48±10.39 ng/g, respectively) than in braised chickens (2.70±9.67 and 0.92 ng/g, respectively). The maximum levels of AαC were in the same proportions in flamed (12.01 ng/g) and braised chickens (14.13 ng/g). Flamed chicken had the highest Trp-P1 content (530.31 ng/g). The 4,8-DiMeIQx was not detected in braised chicken. The AαCs were more abundant in flamed than in braised chicken. The profile and the contents of the HAAs in processed chicken are related to cooking methods. Because of the high variability observed on the obtained concentrations, investigations on the contents of precursors in raw chicken, the effect of marinating ingredients on the formation of HAAs are needed.
| S-EPMC9803208 | biostudies-literature
Project description:Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort.
| S-EPMC3376920 | biostudies-literature
Project description:Since Dr. Sugimura's discovery of heterocyclic aromatic amines (HAA) in broiled fish, many epidemiological studies have been conducted to investigate their role in human cancers, often focusing on colorectal cancer. The difficulty in measuring HAA exposure from meat and fish intake in these studies has resulted in inconsistent findings. Because studying individuals who may be particularly susceptible to the carcinogenic effects of HAA might facilitate the demonstration of a link with cancer, multiple studies have focused on individuals with the high activity phenotype for CYP1A2 and/or NAT2, the two main metabolic enzymes involved in the bioactivation of HAA. These investigations have also yielded inconsistent results. Two recent large pooled analyses of colorectal cancer studies have helped clarify the overall evidence. One was conducted in whites and reported no interaction of red meat intake and NAT2 genotype on risk in Whites. The other was conducted in Japanese and African Americans, two populations with high rates of the disease and a prevalence of the at-risk rapid NAT2 phenotype 10- and 2-fold greater than in whites, respectively. In those groups, a significant interaction was found, with the association of red meat with colorectal cancer being strongest among individuals with the rapid NAT2 phenotype, intermediate among those with the intermediate phenotype and not significant among those with the slow NAT2 phenotype. Recent research on biomarkers has focused on PhIP hair content, as a marker of exposure to HAA, and on DNA adducts using new sensitive quantitative methods, as markers of early biological effects. These advances, when brought to bear, may contribute greatly to the further elucidation of the carcinogenicity of HAA in humans.
| S-EPMC8183058 | biostudies-literature