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A systematic study involving the use and optimization of gas-phase modifiers in quantitative differential mobility-mass spectrometry (DMS-MS) analysis is presented using nucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes, and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 10(6) normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab initio thermochemical results, we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry, but at lower temperatures, multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.

Graphical abstract Highlights • Metal-free one-pot approach to 2-aminobiphenyls. • The direct C(sp2)–H arylation of anilines with diazonium salts. • Eosin Y as an organophotoredox catalyst. • Visible-light-mediated Gomberg-Bachmann reaction. Abstract An efficient, metal-free and highly selective protocol for the synthesis of 2-aminobiphenyls via visible-light-mediated arylation of anilines using aryl diazonium salts (Gomberg-Bachmann reaction) has been reported. The reaction is an example of photoredox catalysed direct C(sp2)–H arylation of anilines using eosin Y as an organophotoredox catalyst. The presented visible-light-mediated environmentally sustainable approach has the potential to earn a decent position among the classical and contemporary methods for the synthesis of aminobiaryls. [ABSTRACT FROM AUTHOR]

Background: This paper describes a simple and sensitive ultra-HPLC–triple quadrupole MS (LC-MS/MS) method for the determination of six unsulfonated aromatic amines in the color additives FD&C Yellow No. 5 (Y5) and FD&C Yellow No. 6 (Y6). The six amines determined by this method are aniline (ANL), benzidine (BNZ), 4-aminobiphenyl (4ABP), 4-aminoazobenzene (4AAB), 2-aminobiphenyl (2ABP), and 4-aminobenzonitrile (4ABN). Objective: This method is intended for use in batch certification of the color additives by the U.S. Food and Drug Administration (FDA) to ensure that each lot meets published specifications for coloring foods, drugs, and cosmetics. Methods: A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure is used for extraction of the amines. Quantitative determination was performed in electrospray positive ionization and multiple-reaction monitoring modes. Results: Validation of the method demonstrated overall recovery of 101–115% and precision of 1.74–9.78% for all analytes. Excellent regression coefficients were obtained, with values >0.999. Conclusions: The validated method was successfully used for the analyses of 30 Y5 and Y6 samples and provided results that are consistent with results from the current method used by FDA, with greater sensitivity and low matrix effects. Highlights: The validation results demonstrate that the new LC-MS/MS method is applicable for use in routine batch certification. [ABSTRACT FROM AUTHOR]

4-Aminobiphenyl (4-ABP) which is primarily formed during tobacco combustion and overheated meat is a major carcinogen responsible for various cancers. Its adducted form, N -deoxyguanosine-C8-4-aminobiphenyl (dG-C8-4-ABP), has long been employed as a biomarker for assessment of the risk for cancer. In this review, the metabolism and carcinogenisity of 4-ABP will be discussed, followed by a discussion of the current common approaches of analyzing dG-C8-4-ABP. The major part of this review will be on the history and recent development of key methods for detection and quantitation of dG-C8-4-ABP in complex biological samples and their biological applications, from the traditional 2 P-postlabelling and immunoassay methods to modern liquid chromatography-mass spectrometry (LC-MS) with the latter as the focus. Many vital biological discoveries based on dG-C8-4-ABP have been published by using the nanoLC-MS with column switching platform in our laboratory, which has also been adopted and further improved by many other researchers. We hope this review can provide a perspective of the challenges that had to be addressed in reaching our present goals and possibly bring new ideas for those who are still working on the frontline of DNA adducts area. [ABSTRACT FROM AUTHOR]

In this work the decolourization of Direct Blue 2 dye (DB2) using an industrial soybean waste as a source of peroxidases was studied. Temperature, pH, amount of H2O2 and concentration of dye were evaluated to determine the maximum catalytic activity of the enzyme during the dye degradation process. It was observed that a temperature of 40°C, a pH of 5 and a concentration of 40 mg/L for the dye in aqueous phase, play a significant role in the overall enzyme-mediated reaction. The maximum decolourization efficiency achieved under optimal conditions was 70% ± 4%. HPLC studies were carried out to confirm dye degradation and analyse the intermediate metabolites. The oxidation products quantified during the reaction were benzidine and 4 aminobiphenyl. Also, an increase in toxicity, determined by Vibrio fisheri, was observed after the enzymatic oxidation of the dye. Results suggest that the oxidation of DB2 with peroxidases can be recommended as a pretreatment step before a conventional treatment process. [ABSTRACT FROM AUTHOR]

The authors describe an ultrasonic-assisted headspace method for solid phase micro-extraction (UA-HS-SPME) of 7 polychlorinated biphenyls (PCBs) with codes PCB28, PCB52, PCB101, PCB118, PCB138, PCB153 and PCB180. The coating is based on a poly-dopamine metal-organic framework [PDA-MIL-53(Fe)] on a stainless steel wire. The coating can be prepared and evenly deposited on the stainless fiber by dipping the PDA fiber into a solution of MIL-53(Fe). The assay is also environmentally friendly because water is used as the solvent. The effects of extraction time, addition of salts, pH value and power of ultrasonic power were optimized. The coating is found to possess a high selectivity and adsorption capacity for PCBs compared to commercial SPME fibers such as the divinylbenzene/carboxen/polydimethylsiloxane fibers. Following desorption, the PCBs were quantified by GC-MS. The detection limits are between 50 and 90 pg⋅g of PCBs in soil. The fibers can be easily prepared, and the batch-to-batch reproducibility (RDS) is <10% (for n = 6). The fibers are inexpensive, re-usable and can be easily manipulated, and particularly well suited for screening polychlorinated biphenyls in soil. [ABSTRACT FROM AUTHOR]

Aromatic amines covalently bound to hemoglobin (Hb) as sulfinamide adducts at the cysteine 93 residue of the Hb β chain have served as biomarkers to assess exposure to this class of human carcinogens for the past 30 years. In this study, we report that 2-amino-9H-pyrido[2,3-b]indole (AαC), an abundant carcinogenic heterocyclic aromatic amine formed in tobacco smoke and charred cooked meats, also reacts with Hb to form a sulfinamide adduct. A novel nanoflow liquid chromatography/ion trap multistage mass spectrometry (nanoLC-IT/MS³) method was established to assess exposure to AαC and the tobacco-associated bladder carcinogen 4-aminobiphenyl (4-ABP) through their Hb sulfinamide adducts. Following mild acid hydrolysis of Hb in vitro, the liberated AαC and 4-ABP were derivatized with acetic anhydride to form the N-acetylated amines, which were measured by nanoLC-IT/MS³. The limits of quantification (LOQ) for AαC- and 4-ABP-Hb sulfinamide adducts were ≤7.1 pg/g Hb. In a pilot study, the mean level of Hb sulfinamide adducts of AαC and 4-ABP were, respectively, 3.4-fold and 4.8-fold higher in smokers (>20 cigarettes/day) than nonsmokers. In contrast, the major DNA adducts of 4-ABP, N-(2'-deoxyguanosin-8-yl)-4-aminobiphenyl, and AαC, N-(2'-deoxyguanosin-8-yl)-2-amino-9H-pyrido[2,3-b]indole, were below the LOQ (3 adducts per 109 bases) in white blood cell (WBC) DNA of smokers and nonsmokers. These findings reaffirm that tobacco smoke is a major source of exposure to AαC. Hb sulfinamide adducts are suitable biomarkers to biomonitor 4-ABP and AαC; however, neither carcinogen binds to DNA in WBC, even in heavy smokers, at levels sufficient for biomonitoring. [ABSTRACT FROM AUTHOR]

Differential pulse voltammetry, cyclic voltammetry, alternating current voltammetry, and chronocoulometry at a hanging mercury drop electrode (HMDE) and DNA modified HMDE were used for the study of the interaction of 4-nitrobiphenyl (4-NBP) with double-stranded DNA and for the detection of DNA damage caused by its interaction with 4-NBP. Moreover, the interaction of DNA with intermediates of the 4-NBP reduction and with 4-aminobiphenyl, a metabolite of 4-NBP, was investigated. The mechanism of the electrochemical reduction of 4-NBP was investigated using CV, too. It was found that the reduction of 4-NBP is controlled by both diffusion and adsorption. The rate constant of the reduction and the diffusion coefficient were calculated as well. [ABSTRACT FROM AUTHOR]

The third generation of aminobiphenyl palladacycle pre-catalyst 'G3-Xantphos' enables functionalization of peptides containing cysteine in high yields. The conjugation (bioconjugation) occurs chemoselectively at room temperature under biocompatible conditions. Extension of the method to protein functionalization allows selective bioconjugation of the trastuzumab antibody. [ABSTRACT FROM AUTHOR]

The use of chemicals to obtain semi-processed leather must be consistent with the environmental laws and regulations, which requires evaluation of toxicity in leather goods intended for consumption. The paper proposes to implement and validate an instrumental analytical method to determine azo dyes in leather. The presence of azo dyes was determined on a total of three restricted aromatic amines (4-aminobiphenyl, benzidine, 5-nitro-o-toluidine), which can be found as a result of the split of dyes used in leather dyeing. Validation parameters of gas chromatographic method were: accuracy (trueness and reliability), precision, sensitivity, limit of detection, limit of quantification, working range, linearity. [ABSTRACT FROM AUTHOR]

ABSTRACT The phase appearance during the synthesis of fluorinated polyamic acid (PAA) from 2,2-bis(3,4-anhydrodicarboxyphenyl)-hexafluoropropane (6FDA) and 2,2′-bis(trifluoromethyl)−4,4′-diaminobiphenyl (TFDB) in supercritical carbon dioxide (scCO2) was investigated to obtain fundamental data for the deposition of fluorinate polyimides (PI) using scCO2. All polymerizations were carried out at 30 MPa for 60 min. The experimental temperatures ranged from 50 to 70 °C, and each of the monomer concentrations ranged from 0.67 × 10−5 to 3.3 × 10−5 mol cm−3. The holding time of the transparent phases, which was the time from the beginning of the polymerization to the appearance of a turbid phase, was increased with either a decrease in the polymerization temperature or a decrease in the initial monomer concentration. The holding time of the fluorinated PAA was longer than that of the monomers of Kapton-type PAA. The deposition of PI into the microscopic-scale trenches that had formed on the silicon wafer was successful in scCO2. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43334. [ABSTRACT FROM AUTHOR]

A broad and efficient regioselective aerobic oxidative cross-coupling of phenols and aniline derivatives in the presence of AgNO 3 and H 2 O 2 resulting in 2′-aminobiphenyl-2-ols has been developed. This reaction is selective toward the creation of a new C C bond at the ortho position to both amine and hydroxyl functional groups in the respective starting materials. Although oxidative cross-coupling of phenols and anilines resulting in 2′-aminobiphenyl-2-ol derivatives have been reported, these reactions have been mainly limited to 2-naphthol and 1-naphthol. This is one of the rare reports in which this type of cross-coupling reaction is expanded to simple phenol derivatives. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering is a useful technique for detecting low levels of aromatic amines as environmental contaminants because it can be used to detect and distinguish among their isomers based on their distinctive SERS spectra. This paper demonstrates the feasibility of measuring the concentrations of aminobiphenyls (ABPs) including 4-ABP, 3-ABP, and 2-ABP down to the levels of about 5, 50, and 250 μg/mL, respectively. The SERS signal intensities of ABPs are dependent on the pH values of the samples and colloidal media. The optimal sample pH values were found to be 6.86, 7.83, and 7.36, for 2-ABP, 3-ABP, and 4-ABP, respectively, whereas the optimum silver colloidal pH ranges from 5.0 to 6.5. A detailed analysis of the different vibrational modes of aniline and the ABP isomers was carried out using computational modeling based on the density functional theory (DFT). Compared to aniline, the ABPs produced greater SERS enhancement of the intensities for the biphenyl ring-breathing mode. The SERS signal for the NH 2 wagging band shows the order of enhancement as given by 4-ABP > 2-ABP > 3-ABP, which correlates well with the HOMO-LUMO energy gap based on the DFT modeling of the amines adsorbed on the silver cluster. [ABSTRACT FROM AUTHOR]

As a continuation to our previous research, twenty-eight aromatic-heterocyclic biphenyls were designed and synthesized as novel Bcr–Abl inhibitors. The title compounds were investigated for their antiproliferative activities against wild K562 cells and Imatinib-resistant K562 cells (K562R). The results indicated that most of them exhibited potent Bcr–Abl inhibition and moderate antiproliferative potency against K562 cells. Furthermore, three compounds 3 , 7 and 21 displayed moderate antiproliferative activities against K562R cells. Molecular docking indicated that 3 bound more tightly with Bcr–Abl T315I compared to Bcr–Abl WT . The higher affinity was consistent with its relatively promising K562R cell growth inhibition. These aromatic-heterocyclic biphenyls could be considered as novel lead compound for optimized as Bcr–Abl T315I inhibitors. They provide a good starting point for the further development of novel anti-leukemia agents capable of dealing with clinical acquired resistance against Imatinib. [ABSTRACT FROM AUTHOR]

4-Aminobiphenyl (ABP) is a trace component of cigarette smoke and hair dyes, a suspected human carcinogen and a potent rodent liver carcinogen. Postnatal exposure of mice to ABP results in a higher incidence of liver tumors in males than in females, paralleling the sex difference in human liver cancer incidence. A traditional model of ABP tumorigenesis involves initial CYP1A2-mediated N-hydroxylation, which eventually leads to production of mutagenic ABP-DNA adducts that initiate tumor growth. However, several studies have found no correlation between sex or CYP1A2 function and the DNAdamaging, mutagenic, or tumorigenic effects of ABP. Oxidative stress may be an important etiological factor for liver cancer, and it has also been linked to ABP exposure. The goals of this study were to identify novel enzyme(s) that contribute to ABP N-oxidation, and to investigate a potential role for oxidative stress in ABP liver tumorigenicity. Isozyme-selective inhibition experiments using liver microsomes from wild-type and genetically modified mice identified CYP2E1 as a major ABP N-hydroxylating enzyme. The N-hydroxylation of ABP by transiently expressed CYP2E1 produced oxidative stress in cultured mouse hepatoma cells. In uiuo postnatal exposure of mice to a tumorigenic dose of ABP also produced oxidative stress in male wild-type mice, but not in male Cyp2el(-/-) mice or in female mice. However, a stronger NRF2-associated antioxidant response was observed in females. Our results identify CYP2E1 as a novel ABP-N-oxidizing enzyme, and suggest that sex differences in CYP2E1-dependent oxidative stress and antioxidant responses to ABP may contribute to the observed sex difference in tumor incidence. [ABSTRACT FROM AUTHOR]

ABSTRACT 2-Aminobiphenyls (2-ABP) induces oxidative DNA damage and leads to apoptosis. The precise signaling pathways of inducing apoptosis in vitro are still unknown. This study provides insight into the relationship between 2-ABP-induced apoptosis and the activation of MAPK and downstream transcription factors using pharmacological inhibitors of ERK, p38, and JNK pathways. Results showed that 2-ABP induced the activation of ERK and JNK but not p38. The ERK/JNK pathways downstream transcription factors, c-Jun and ATF-2, were also activated by 2-ABP. The inhibitory effects of ERK inhibitor, U0126, on 2-ABP-induced caspase-3 activity were not detected. However, JNK inhibitor, SP600125, significantly attenuated the caspase-3 activity induced by 2-ABP. The expression of the transcription factors c-Jun and ATF-2 were decreased in 2-ABP treated cells in the presence of ERK/JNK inhibitors, suggesting that the expression of ERK/JNK pathways leads to the downstream activation of c-Jun and ATF-2. N-acetylcysteine, an ROS scavenger, inhibited 2-ABP-induced activation of ERK and JNK, the cell death and caspase-3 activity, which suggested that oxidative stress plays a crucial role in apoptosis through activation of caspase-3 in a ROS/JNK-dependent signaling cascade. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 205-211, 2015. [ABSTRACT FROM AUTHOR]

Covalent post-synthetic modification is a versatile method for gaining high-level synthetic control over functionality within porous metal-organic frameworks and for generating new materials not accessible through one-step framework syntheses. Here we apply this topotactic synthetic approach to a porous spin crossover framework and show through detailed comparison of the structures and properties of the as-synthesised and covalently modified phases that the modification reaction proceeds quantitatively by a thermally activated single-crystal-to-single-crystal transformation to yield a material with lowered spin-switching temperature, decreased lattice cooperativity, and altered color. Structure-function relationships to emerge from this comparison show that the approach provides a new route for tuning spin crossover through control over both outer-sphere and steric interactions. [ABSTRACT FROM AUTHOR]

Abstract: We examined the role of miRNAs in DNA damage response in HepG2 cells following exposure to 4-aminobiphenyl (4-ABP). The arylamine 4-ABP is a human carcinogen. Using the Comet assay, we showed that 4-ABP (18.75–300μM) induces DNA damage in HepG2 cells after 24h. DNA damage signaling pathway-based PCR arrays were used to investigate expression changes in genes involved in DNA damage response. Results showed down-regulation of 16 DNA repair-related genes in 4-ABP-treated cells. Among them, the expression of selected six genes (UNG, LIG1, EXO1, XRCC2, PCNA, and FANCG) from different DNA repair pathways was decreased with quantitative real-time PCR (qRT-PCR). In parallel, using the miRNA array, we reported that the expression of 27 miRNAs in 4-ABP-treated cells was at least 3-fold higher than that in the control group. Of these differential 27 miRNAs, the most significant expression of miRNA-513a-5p and miRNA-630 was further validated by qRT-PCR, and was predicted to be implicated in the deregulation of FANCG and RAD18 genes, respectively, via bioinformatic analysis. Both FANCG and RAD18 proteins were found to be down-regulated in 4-ABP-treated cells. In addition, overexpression and knockdown of miRNA-513a-5p and miRNA-630 reduced and increased the expression of FANCG and RAD18 proteins, respectively. Based on the above results, we indicated that miRNA-513a-5p and miRNA-630 could play a role in the suppression of DNA repair genes, and eventually lead to DNA damage. [Copyright &y& Elsevier]

A series of phosphine-ligated palladium precatalysts based on N-methyl- and N-phenyl-2-aminobiphenyl have been developed. Substitution at the nitrogen center prevents the presence of traces of aminobiphenyls that contain a free -NH2 group from contaminating cross-coupling products. These precatalysts produce N-substituted carbazoles upon activation, which cannot consume starting materials. These precatalysts were efficiently generated from 2-aminobiphenyl with minimal purification and found to be highly effective in Suzuki-Miyaura and C-N cross-coupling reactions. [ABSTRACT FROM AUTHOR]

4-Aminobiphenyl (4-ABP), an aromatic amine is a major environmental carcinogen found mainly in cigarette smoke. It has been vastly implicated in mutagenesis and cancer development. In this study, commercially available human placental DNA was exposed to 4-ABP (1.3 mM) in presence of sodium nitroprusside (SNP; 8 mM) at 37°C for 3 h. The 4-ABP + SNP-mediated structural changes in human DNA were studied by ultraviolet, circular dichroism and fluorescence spectroscopy, thermal melting profile, agarose gel electrophoresis, and nuclease S1 digestibility assay. Spectroscopical analysis and melting temperature studies suggest structural perturbations in the DNA as a result of modification. This might be due to generation of single-stranded regions and destabilization of hydrogen bonds. Modification was also visualized in agarose gel electrophoresis. Furthermore, nuclease S1 digestibility confirmed the generation of single strand breaks. Rabbits challenged with 4-ABP-SNP-modified human DNA-induced high-titer immunogen-specific antibodies, which showed Cross-reaction with modified/unmodified DNA bases and ss-DNA in competitive inhibition assay. The immunogen specificity of induced antibodies against 4-ABP-SNP-modified human DNA was further confirmed in gel retardation assay. It may be concluded that induction of anti-modified DNA antibodies could be due to perturbation in the DNA structure and its subsequent recognition by immunoregulatory cells as a foreign molecule. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 568-576, 2014. [ABSTRACT FROM AUTHOR]

Substituted 2-aminobiphenyls have been prepared from arylhydrazine hydrochlorides and anilines in biphasic radical arylation reactions with dioxygen from air as a most simple and readily available oxidant. Under optimized conditions, the free amino functionality of the aniline leads to high ortho:meta regioselectivities, now even for anilines bearing a donor substituent in the para position. Finally, the mild and metal-free new access to aminobiphenyls was shown to be applicable on a gram scale. [ABSTRACT FROM AUTHOR]

An SPE cartridge based on an ampholine-functionalized hybrid organic-inorganic silica sorbent has been adopted for the analysis of aromatic amines including 4-aminobiphenyl, benzidine, 2-naphthylamine, p-chloroaniline, 2,4,5-trimethylaniline, and 3,3′-dichlorobenzidine. Crucial variables governing the extraction efficiency of the material such as the pH of sample, sample loading volume, solvent used for elution, and elution volume have been thoroughly optimized. The adsorption capacities for the six aromatic amines ranged from 0.17 to 1.82 μg/mg. The recoveries of aromatic amines spiked in textile samples ranged from 78.9 to 103.0%, with RSDs of 1.1-11.9% ( n = 3). Moreover, the extraction efficiency of the ampholine-functionalized hybrid organic-inorganic silica sorbent was at least comparable with that of Oasis WCX. [ABSTRACT FROM AUTHOR]

Highlights: [•] Non-isothermal pyrolysis of amino acid and tobacco with amino acid was conducted. [•] Samples were non-isothermally pyrolyzed at up to 800°C under N2 flow. [•] Polycyclic aromatic amines in each pyrolysis product were determined. [•] Amino acids would work as donators of amine-moieties in co-pyrolysis with tobacco. [•] Aryl moiety in phenylalanine would supply the building blocks for aminobiphenyls. [ABSTRACT FROM AUTHOR]

Humans are exposed to carcinogenic chemicals via occupational and environmental exposures. Common chemicals of concern that can occur in exposures together are aromatic amines (e.g., 4-aminobiphenyl [4-ABP] and β-naphthylamine [BNA]) and hexavalent chromium (Cr[VI]). Arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) are key to the metabolism of aromatic amines and their genotoxicity. The effects of Cr(VI) on the metabolism of aromatic amines remains unknown as well as how it may affect their ensuing toxicity. The objective of the research presented here is to investigate the effects of Cr(VI) on the metabolism and genotoxicity of 4-ABP and BNA in immortalized human lung epithelial cells (BEP2D) expressing NAT1 and NAT2. Exposure to Cr(VI) for 48 h increased NAT1 activity (linear regression analysis: P < 0.0001) as measured by N-acetylation of para-aminobenzoic acid (PABA) in BEP2D cells but not NAT2 N-acetylation of sulfamethazine, which are prototypic NAT1 and NAT2 substrates respectively. Cr(VI) also increased the N-acetylation of 4-ABP and BNA. In BEP2D cells the N-acetylation of 4-ABP (1-3 μM) exhibited a dose-dependent increase (linear regression analysis: P < 0.05) following co-incubation with 0-3 μM Cr(VI). In BEP2D cells, incubation with Cr(VI) caused dose-dependent increases (linear regression analysis: P < 0.01) in expression of CYP1A1 protein and catalytic activity. For genotoxicity, BEP2D cells were exposed to 4-ABP or BNA with/without Cr(VI) for 48 h. We observed dose-dependent increases (linear regression analysis: P < 0.01) in phospho-γH2AX protein expression for combined treatment of 4-ABP or BNA with Cr(VI). Further using a CYP1A1 inhibitor (α-naphthoflavone) and NAT1 siRNA, we found that CYP1A1 inhibition did not reduce the increased N-acetylation or genotoxicity of BNA by Cr(VI), while NAT1 inhibition did reduce increases in BNA N-acetylation and genotoxicity by Cr(VI). We conclude that during co-exposure of aromatic amines and Cr(VI) in human lung cells, Cr(VI) increased NAT1 activity contributing to increased 4-ABP and BNA genotoxicity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Electrocatalytic oxidation (EO) of carcinogenic 4-aminobiphenyl (4-ABP) aromatic amine was performed using Ti-RuO 2 anodes. Current (I), pH, electrolysis time (t), and 4-ABP initial concentration (C o ) were selected as EO parameters, and their effects on %4-ABP removal (R 1 ) and energy consumed (R 2 ) were studied. Experimental design, parameters optimization, and their interaction with responses R 1 and R 2 were performed using response surface methodology. At optimized parameters, %TOC removal and 4-BP mineralization current efficiency (%MCE) were assessed to evaluate the potential of Ti/RuO 2 anodes towards 4-ABP mineralization. Simultaneous TOC and 4-ABP degradation kinetics were also studied to evaluate the competition in 4-ABP mineralization and degradation. Further, UPLC-Q-TOF-MS analysis was performed to identify the 4-ABP transformation products during the EO, and a mechanism describing the EO transformation was proposed. At optimum parameters (I = 1.2 A; pH = 4.0; t = 30 min; C o  = 30 ppm), responses were found to be R 1  = 60.25%; R 2  = 2.49 kWh/g of 4-ABP removed. %TOC removal and %MCE were 52.4% and 34.2%, respectively. PRACTITIONER POINTS: 4-Aminobiphenyl electro-oxidation (EO) was explored using Ti/RuO 2 anode. Achieved 34.2% mineralization current efficiency, 52.4% TOC and 61.3% TKN removal. Three electro-oxidation transformation products of 4-ABP were detected. 4-Aminobiphenyl was found degrading at ≈1.6 times higher rate than TOC A plausible EO transformation pathway and mechanism was proposed., (© 2022 Water Environment Federation.)

One model for cancer initiation by 4-aminobiphenyl (ABP) involves N-oxidation by cytochrome P450 CYP1A2 followed by O-conjugation by N-acetyltransferase(s) NAT1 and/or NAT2 and decomposition to a DNA-binding nitrenium ion. We recently observed that neonatal ABP exposure produced liver tumors in male but not in female mice, and that NAT deficiency reduced liver tumor incidence. However, ABP-induced liver tumor incidence did not correlate with liver levels of N-(deoxyguanosin-8-yl)-ABP adducts 24 hr after exposure. In this study, we compared in vivo ABP-induced DNA mutant frequencies and spectra between male and female wild-type and NAT-deficient Muta™Mouse using both the tumor-inducing neonatal exposure protocol and a 28-day repetitive dosing adult exposure protocol. ABP produced an increase in liver DNA mutant frequencies in both neonates and adults. However, we observed no sex or strain differences in mutant frequencies in neonatally exposed mice, and higher frequencies in adult females than males. Neonatal ABP exposure of wild-type mice increased the proportion of G-T transversions in both males and females, while exposure of Nat1/2(-/-) mice produced increased G-T transversions in males and a decrease in females, even though females had higher levels of N-(deoxyguanosin-8-yl)-4-ABP adducts. There was no correlation of mutant frequencies or spectra between mice dosed as neonates or as adults. These results suggest that observed sex- and NAT-dependent differences in ABP-induced liver tumor incidence in mice are not due to differences in either mutation rates or mutational spectra, and that mechanisms independent of carcinogen bioactivation, covalent DNA binding and mutation may be responsible for these differences. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We describe how we have been able to design 4-aminobiphenylsthatare nonmutagenic (inactive in the Ames test). No such 4-aminobiphenylswere known to us, but insights provided by quantum mechanical calculationshave permitted us to design and synthesize some examples. Importantly,the quantum mechanical calculations could be combined with predictionsof other properties of the compounds that contained the 4-aminobiphenylsso that these remained druglike. Having found compounds that are notactive, the calculations can provide insight into which factors (electronicand conformational in this case) are important. The calculations providedSAR-like information that was able guide the design of further examplesof 4-aminobiphenyls that are not active in the Ames test. [ABSTRACT FROM AUTHOR]

4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy- N-acetyl-4-aminobiphenyl ( N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study, human placental DNA was modified with N-OH-AABP, and the structural perturbations in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1 digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing female rabbits. The modified DNA was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies, while the native form was almost nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in recognizing various nucleic acid conformers and DNA bases. We also detected deposits of immune complex in glomerular basement membrane in rabbits immunized with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies in cancer patients and the related consequences have been discussed. © 2012 IUBMB Life, 64(4): 340-345, 2012 [ABSTRACT FROM AUTHOR]

N2-Hydrazinoaryl and N2-azoaryl-dG adducts of borderline carcinogens and the bladder and breast carcinogen 4-aminobiphenyl were prepared using Pd-catalyzed cross-coupling chemistry. After conversion into the phosphoramidites site-specifically damaged oligonucleotides were prepared by automated DNA synthesis. DNA Hybrids were studied with respect to their thermal stability (UV melting-temperature analysis) and circular dichroism. [ABSTRACT FROM AUTHOR]