Metabolism Of Polycyclic Aromatic Hydrocarbons Research Articles

Environmental significance of PAH photoproduct formation: TiO2 nanoparticle influence, altered bioavailability, and potential photochemical mechanisms

Interactions between polycyclic aromatic hydrocarbons (PAHs) and titanium dioxide (TiO2) nanoparticles (NPs) can produce unforeseen photoproducts in the aqueous phase. Both PAHs and TiO2-NPs are well-studied and highly persistent environmental pollutants, but the consequences of PAH-TiO2-NP interactions are rarely explored. We investigated PAH photoproduct formation over time for benzo[a]pyrene (BaP), fluoranthene (FLT), and pyrene (PYR) in the presence of ultraviolet A (UVA) using a combination of analytical and computational methods including, identification of PAH photoproducts, assessment of expression profiles for gene indicators of PAH metabolism, and computational evaluation of the reaction mechanisms through which certain photoproducts might be formed. Chemical analyses identified diverse photoproducts, but all PAHs shared a primary photoproduct, 9,10-phenanthraquinone (9,10-PQ), regardless of TiO2-NP presence. The computed reaction mechanisms revealed the roles photodissociation and singlet oxygen chemistry likely play in PAH mediated photochemical processes that result in the congruent production of 9,10-PQ within this study. Our investigation of PAH photoproduct formation has provided substantial evidence of the many, diverse and congruent, photoproducts formed from physicochemically distinct PAHs and how TiO2-NPs influence bioavailability and time-related formation of PAH photoproducts.

Activity-Based Protein Profiling to Probe Relationships between Cytochrome P450 Enzymes and Early-Age Metabolism of Two Polycyclic Aromatic Hydrocarbons (PAHs): Phenanthrene and Retene.

A growing body of literature has linked early-life exposures to polycyclic aromatic hydrocarbons (PAH) with adverse neurodevelopmental effects. Once in the body, metabolism serves as a powerful mediator of PAH toxicity by bioactivating and detoxifying PAH metabolites. Since enzyme expression and activity vary considerably throughout human development, we evaluated infant metabolism of PAHs as a potential contributing factor to PAH susceptibility. We measured and compared rates of phenanthrene and retene (two primary PAH constituents of woodsmoke) metabolism in human hepatic microsomes from individuals ≤21 months of age to a pooled sample (n = 200) consisting primarily of adults. We used activity-based protein profiling (ABPP) to characterize cytochrome P450 enzymes (CYPs) in the same hepatic microsome samples. Once incubated in microsomes, phenanthrene demonstrated rapid depletion. Best-fit models for phenanthrene metabolism demonstrated either 1 or 2 phases, depending on the sample, indicating that multiple enzymes could metabolize phenanthrene. We observed no statistically significant differences in phenanthrene metabolism as a function of age, although samples from the youngest individuals had the slowest phenanthrene metabolism rates. We observed slower rates of retene metabolism compared with phenanthrene also in multiple phases. Rates of retene metabolism increased in an age-dependent manner until adult (pooled) metabolism rates were achieved at ∼12 months. ABPP identified 28 unique CYPs among all samples, and we observed lower amounts of active CYPs in individuals ≤21 months of age compared to the pooled sample. Phenanthrene metabolism correlated to CYPs 1A1, 1A2, 2C8, 4A22, 3A4, and 3A43 and retene metabolism correlated to CYPs 1A1, 1A2, and 2C8 measured by ABPP and vendor-supplied substrate marker activities. These results will aid efforts to determine human health risk and susceptibility to PAHs exposure during early life.

Cardiolipin Membranes Promote Cytochrome c Transformation of Polycyclic Aromatic Hydrocarbons and Their In Vivo Metabolites.

The catalytic properties of cytochrome c (Cc) have captured great interest in respect to mitochondrial physiology and apoptosis, and hold potential for novel enzymatic bioremediation systems. Nevertheless, its contribution to the metabolism of environmental toxicants remains unstudied. Human exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with impactful diseases, and animal models have unveiled concerning signs of PAHs' toxicity to mitochondria. In this work, a series of eight PAHs with ionization potentials between 7.2 and 8.1 eV were used to challenge the catalytic ability of Cc and to evaluate the effect of vesicles containing cardiolipin mimicking mitochondrial membranes activating the peroxidase activity of Cc. With moderate levels of H2O2 and at pH 7.0, Cc catalyzed the oxidation of toxic PAHs, such as benzo[a]pyrene, anthracene, and benzo[a]anthracene, and the cardiolipin-containing membranes clearly increased the PAH conversions. Our results also demonstrate for the first time that Cc and Cc-cardiolipin complexes efficiently transformed the PAH metabolites 2-hydroxynaphthalene and 1-hydroxypyrene. In comparison to horseradish peroxidase, Cc was shown to reach more potent oxidizing states and react with PAHs with ionization potentials up to 7.70 eV, including pyrene and acenaphthene. Spectral assays indicated that anthracene binds to Cc, and docking simulations proposed possible binding sites positioning anthracene for oxidation. The results give support to the participation of Cc in the metabolism of PAHs, especially in mitochondria, and encourage further investigation of the molecular interaction between PAHs and Cc.

Exposure to polycyclic aromatic hydrocarbons increases the risk of poor sleep pattern in US adults: results from the NHANES (2005-2010).

Recently, polycyclic aromatic hydrocarbons (PAHs) were found to be linked to various diseases. The current study's objective was to explore whether or not there was a relation between PAH exposure and poor sleep pattern. We evaluated nine urine PAH metabolites as exposures in our cross-sectional research based on the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Logistic regression, restricted cubic spline regression (RCS) model, weighted quantile sum (WQS) regression, subgroup analysis, and mediation analysis were used to assess the associations between PAH metabolism and poor sleep pattern risk. After controlling for all confounding variables, several primary PAH metabolites, namely 1-hydroxynapthalene (1-NAP, OR 1.32, 95% CI 1.04-1.68), 2-hydroxyfluorene (2-FLU, OR 1.34, 95% CI 1.05-1.71), 1-hydroxyphenanthrene (1-PHE, OR 1.30, 95% CI 1.03-1.64), 9-hydroxyfluorene (9-FLU, OR 1.38, 95% CI 1.09-1.74), and ∑PAHs (OR 1.33, 95% CI 1.05-1.69), compared to the bottom tertile, were associated with increased risk of poor sleep pattern. The WQS regression analysis showed that 9-FLU and 1-NAP comprised the two most important factors related to poor sleep pattern. Mediation analysis revealed that inflammation acted as a mediator between PAHs and the prevalence of poor sleep pattern. In conclusion, exposure to PAHs may be associated with poor sleep pattern. Inflammation is a mediator of the effects of PAH exposure on poor sleep pattern.

Bacterial cell sensing and signaling pathway for external polycyclic aromatic hydrocarbons (PAHs)

The mechanism by which a bacterial cell senses external nutrients remains largely unknown. In this study, we identified a bacterial cell sensing system for polycyclic aromatic hydrocarbons (PAHs) in a common marine PAH-using bacterium, Cycloclasticus. It consists of an outer membrane receptor (PahS) and a periplasmic protein (PahP) in combination with a two-component sensing system (TCS) that ensures a rapid response to PAH occurrence by directly controlling serial reactions including chemotactic sensing and movement, PAH uptake and intracellular PAH metabolism. PahS protrudes from the cell and acts as a PAH sensor, transducing the PAH signal across the outer membrane to its periplasmic partner PahP, which in turn transduces the PAH signal across the periplasm to a specialized TCS. This sensing system plays a critical role in sensing and promoting the metabolism of PAHs, which can be scavenged by various hydrocarbon-degrading bacteria.

Multi-omics analyses reveal metabolic pathways of benzo[a]pyrene biodegradation under sole or mixed carbon sources

Proteomics and metabolomics can be used to efficiently and conveniently assess proteins and metabolites during microbial degradation of pollutants; these analytical techniques are closely correlated and mutually confirmed and provide a means to explore degradation pathways. The degradation pathways and regulatory characteristics of Microbacterium sp. M. CSW3 for the metabolism of benzopyrene (BaP) alone and in the presence of phenanthrene and pyrene were investigated using these omics. Proteomics results showed that CLP protease, ABC transporter, aldehyde dehydrogenase, and enoyl-CoA hydratase were important for the metabolism of polycyclic aromatic hydrocarbons (PAHs). Five pathways for the microbial degradation of benzopyrene were suggested by metabolomics, and phenanthrene was identified as an intermediate metabolite. Further, correlation analysis showed that the two stress environments inhibited the biosynthesis of bacterial amino acids. The glycolysis/gluconeogenesis and fatty acid degradation pathways played a positive role in energy acquisition and PAHs degradation. Addition of low-molecular-weight PAHs promoted the production of related enzyme systems and also made the degradation of BaP more thorough. This study provides efficient concepts and methods for the exploration of degradation mechanisms of high-molecular-weight PAHs and co-metabolism of mixed PAHs.

Metabolism and elimination kinetics of mono-hydroxylated PAHs metabolites following single exposure to different combinations of PAH4 in rats.

The metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague-Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture.

14 The Development and Characterisation of Novel Monoclonal Antibodies (Mabs) for 1-Hydroxypyrene Glucuronide (1-OHPyrG) Determination and Polycyclic Aromatic Hydrocarbon (PAH) Biomonitoring

Abstract Objective PAHs are produced during the incomplete burning of organic materials. PAH sources include vehicle exhaust, tobacco smoke and waste incineration. Cancer is a significant endpoint of PAH exposure. Pyrene is a common component of PAH exposures and metabolism of pyrene leads to the excretion of 1-OHPyrG in urine. Measurement of 1-OHPyrG has been used to assess occupational and environmental exposure to PAHs. The production of Mabs to 1-OHPyrG will allow the development of novel PAH biomonitoring tests, facilitating the introduction of routine screening and safeguarding human health. Methods 1-Pyrenebutyric acid was coupled to a carrier protein and a sheep Mab raised to 1-OHPyrG. A second Mab which binds the Mab-1-OHPyrG immune complex was also produced and a novel urinary non-competitive ELISA developed. Careful formulation of assay buffers has overcome the heterogeneous nature of urine. Assay performance was confirmed through binding studies with structurally similar metabolites, reproducibility testing and a comparative method study. Results A sensitive and specific ELISA (measuring range 20-500pg/ml) was used to detect elevated levels of 1-OHPyrG in urine. Occupational samples determined by ELISA and HPLC-fluorescence were in good agreement (R2=0.91, N=20). A test kit is now being transferred to manufacture. Conclusions The development of a novel ELISA for 1-OHPyrG has allowed the production of a sensitive and specific PAH biomonitoring test kit. Kits increase the accessibility of biomonitoring and facilitate the introduction of routine screening. Alternate assay formats are being investigated. A lateral flow “point of care” test will enable on-site testing and significantly increase the utility of biomonitoring.

69 Activation of the Aryl Hydrocarbon Receptor - a Major mode of Combustion Particle Toxicity?

Abstract Combustion-derived particles constitute an important part of the fine fraction of particulate matter with aerodynamic diameter less than 2.5 microns (PM2.5) and are considered central for the adverse effects of air pollution. Understanding the mechanisms of combustion particle toxicity may shed light on the components and characteristics of outdoor air PM driving adverse health effects. This may also enable more targeted and efficient policies to improve air quality and promote health and wellbeing. The aryl hydrocarbon receptor (AhR) is a ligand dependent transcription factor, originally discovered for its ability to bind polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds and regulate PAH metabolism. It is now clear that AhR regulates a variety of biological and toxicological responses, overlapping to a considerable degree with the effects of combustion PM and ambient PM2.5. Studies from our lab and others also suggest that AhR activation is among the most sensitive responses to combustion PM exposure, induced at orders of magnitude lower concentrations than many other endpoints. This talk will discuss the potential role of the AhR and PAHs in combustion PM toxicity based on previous and ongoing work, with a main focus on intracellular signalling and regulation of inflammatory reactions in lung epithelial cells and vascular endothelial cells.

Characterization of polycyclic aromatic hydrocarbon (PAH) degrading bacteria and optimization of physicochemical conditions for the production of catechol 1, 2-dioxygenase

Biodegradation of recalcitrant polycyclic aromatic hydrocarbons (PAHs) is highly dependent on the activities of catabolic enzyme and the conditions for metabolism. The most significant studies on process optimization of conditions for catechol 1, 2 dioxygenase (C120) metabolism of PAHs used “one variable at a time” (OVAT) method, however, with its limitations. In this study, optimization of conditions for optimal C12O metabolism of PAH pollutants using the central composite design (CCD) of response surface methodology (RSM) was used. Enrichment technique using mineral salt medium (MSM) was used to isolate bacteria from oil-polluted water and soil milleu from Awoye community in Nigeria. Thereafter, the bacterial isolates were primarily screened through growth on mineral salt medium plates supplemented with (100 - 200) mM catechol and were subjected to secondary screening based on their initial catechol 1, 2-dioxygenase activity. Molecular tools were used to identify the isolate. Amongst the five (5) bacterial isolates acquired from primary screening, it was found that the cell free extract from isolate FEP B16a displayed the highest enzyme activity. Additionally, isolate FEP B16a was able to grow on MSM plate with 200 mM catechol. Based on CCD of RSM, the C12O produced from isolate FEP B16a had maximum activity at 35 ℃, pH 8.0, and 80μM of catechol. Molecular analysis confirmed it as a strain of Microbacterium hydrothermale FEP_B16a. This study concluded that CCD of RSM may be an efficient method to optimize C12O activity over the conventional approach of using single variable at a time.

Deep relationships between bacterial community and polycyclic aromatic hydrocarbons in soil profiles near typical coking plants.

Bacterial communities play an important role in maintaining the normal functioning of ecosystems; therefore, it is important to understand the effects of polycyclic aromatic hydrocarbons (PAHs) on the bacterial community. In addition, understanding the metabolic potential of bacterial communities for PAHs is important for the remediation of PAH-contaminated soils. However, the deep relationship between PAHs and bacterial community in coking plants is not clear. In this study, we determined the bacterial community and the concentration of PAHs in three soil profiles contaminated by coke plants in Xiaoyi Coking Park, Shanxi, China, using 16S rRNA and gas chromatography coupled with mass spectrometry, respectively. The results show that 2 ~ 3 rings PAHs are the main PAHs and Acidobacteria (23.76%) was the dominant bacterial community in three soil profiles. Statistical analysis showed that there were significant differences in the composition of bacterial communities at different depths and different sites. Redundancy analysis (RDA) and variance partitioning analysis (VPA) illustrate the influence of environmental factors (including PAHs, soil organic matter (SOM), and pH) on the vertical distribution of soil bacterial community, and PAHs were the main factors affecting the bacterial community in this study. The co-occurrence networks further indicated correlations between bacterial community and PAHs and found that Nap has the greatest effect on bacterial community compared with other PAHs. In addition, some operational taxonomic units (OTUs, OTU2, and OTU37) have the potential to degrade PAHs. PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used for further study on the potential of microbial PAHs degradation from a genetic perspective, which showed that different PAH metabolism genes were present in the genomes of bacterial communities in the three soil profiles, and a total of 12 PAH degradation-related genes were isolated, mainly dioxygenase and dehydrogenase genes.

Polymorphisms in gene UGT1A1 modify the association of prenatal exposure to polycyclic aromatic hydrocarbons with congenital heart diseases risk

Introduction Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for the occurrence of congenital heart diseases (CHDs). Genetic susceptibility to PAHs metabolism may modify the exposure–risk relationship. The role of uridine diphosphoglucuronosyl transferase 1A1 (UGT1A1) genetic polymorphisms for modulating the impacts of prenatal PAHs exposure on the risk of CHDs remains to be discovered. Objective The aim of this study was to investigate whether maternal UGT1A1 genetic polymorphisms are associated with fetal susceptibility to CHDs and to assess whether the risk is modified by maternal PAHs exposure. Methods Maternal urinary biomarker of PAHs exposure was determined in 357 pregnant women with CHDs fetuses and 270 controls (pregnant women carrying fetuses without major congenital malformations). Urinary 1-hydroxypyrene-glucuronide (1-OHPG) concentration, a sensitive biomarker for PAHs exposure, was measured using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Maternal single nucleotide polymorphisms (SNPs) in UGT1A1, including rs3755319, rs887829, rs4148323, rs6742078, and rs6717546, were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. Unconditional logistic regression was performed to determine the impacts of UGT1A1 polymorphisms on the risks of CHDs and their subtypes. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–PAHs exposure interactions. Results None of the selected UGT1A1 polymorphisms was independently associated with the risk of CHDs. The interaction between SNP rs4148323 and PAHs exposure was observed to be associated with CHDs (p< .05). Pregnant women with high-level PAHs exposure and rs4148323 had an increased risk of carrying CHDs fetuses (GA-AA vs. GG: aOR = 2.00, 95% CI = 1.06–3.79). Moreover, the joint effect of rs4148323 and PAHs exposure was found to be significantly associated with risks of septal defects, conotruncal heart defects, and right-sided obstructive malformations. Conclusions Maternal genetic variations of UGT1A1 rs4148323 may modify the association between prenatal PAHs exposure and CHDs risk. This finding needs to be further confirmed in a larger-scale study.

Combined biological effects of polystyrene microplastics and phenanthrene on Tubifex tubifex and microorganisms in wetland sediment

Microplastics, as emerging pollutants, can adsorb polycyclicaromatic hydrocarbons (PAHs) in aqueous environments. However, the coeffects of PAHs and microplastics on aquatic organisms are vague. In this study, nanoscale and micron-scale microplastics (30 mg/kg) and phenanthrene (10 mg/kg) were added to aquatic sediment to explore the effects of different particle sizes of microplastics and typical PAHs on invertebrates (Tubifex tubifex) and microbes after 28 days operation. The fluorescence signal of fluorescently labelled micron-scale and nanoscale microplastics were detected in T. tubifex, especially nanoscale microplastics. The reduced activities of CAT, GST, SOD and MDA in T. tubifex suggested that the micron-sized microplastics and PAHs exacerbated the oxidative damage to T. tubifex. Microbial analysis confirmed that microplastics and PAHs decreased the abundance of Proteobacteria, Fusobacteriota and Bacteroidetes in the gut of T. tubifex and thereby affected the degradation of phenanthrene. Microplastics also reduced the abundance of Bacteroidetes, Acidobacteria and Proteobacteria in sediment. The abundance of salicylate hydroxylase enzyme that related to PAHs metabolism was increased with the addition of phenanthrene. The results in this study would be useful for further risk assessment of PAHs and microplastics in aquatic environments.

Hepatic genomic assessment of dietary ingestion of 2-aminoanthracene in Sprague Dawley rats

This research aims to investigate the effects of 2-aminoanthracene (2-AA), a polycyclic aromatic hydrocarbon (PAH), on the liver. PAH is a by-product of the incomplete combustion of fossil fuels. Specifically, the impact of 2-AA on different body tissues in animals has been reported. The liver is an organ central to the metabolism of PAHs, including 2-AA. Sprague Dawley rats ingested a well-defined dose of 2-AA in their diet (0, 50, and 100 mg/kg 2-AA) for 12 weeks. Hepatic global gene expression using Affymetrix Rat Genome 230 2.0 microarray was performed. Overall, more than 17,000 genes were expressed. Approximately 70 genes were upregulated, while 65 were downregulated when control rats were compared with low-dose animals. Similarly, 103 genes were upregulated and 49 downregulated when the high-concentration 2-AA group was compared with the control group rats. This result suggests that the magnitude of gene expression fold change depends on the dose of 2-AA ingested. Several differentially expressed genes are involved in biological processes such as gene transcription, cell cycle, and immune system function, indicating that the ingestion of 2-AA could impact these processes. The over-expression of genes related to liver inflammation, nonalcoholic liver disease, hepatic glucose processing, and PAH metabolism were noted.

Reactions

UNDERGRADUATE EDUCATION Reactions ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2023, 101 (7), p 3February 27, 2023Cite this:C&EN 101, 7, 3Letters to the editorOrganic chemistryAs a footnote to Mark M. Green’s letter on how to make organic chemistry “be part of understanding the wider world, to be worth knowing” (Jan. 2, 2023, page 3), I wish to illustrate my approach to “a great story to be told.”For over 50 years I have incorporated five special topics in my sophomore organic chemistry courses starting on day 1. “Chemical Evolution” looks at the simple chemicals and chemical reactions occurring in our universe, Stanley Miller’s exotic prebiotic syntheses of amino acids and peptides, and the simple organic compounds recently found on comets and meteorites. “Insect Pheromones” is introduced during the discussion of alkanes and alkenes, with examples like muscalure, the long-chain alkene of the housefly sex pheromone (a Wittig reaction synthesis), and illustrated by the syntheses of the queen bee pheromone and the Japanese beetle sex pheromone. Halogen addition reactions of alkenes that occur in the ocean via bromonium ions are examples of the natural halogenated alkanes produced by seaweeds (the smell of the ocean), including 1,2-bromochloroalkanes formed when oceanic chloride attacks a bromonium ion generated by bromoperoxidase. “Pesticides and Herbicides” includes the natural insecticides rotenone, caffeine, pyrethrins, and cocaine. Pyrethrins are naturally occurring cyclopropanes, and physostigmine, the “drug of divine justice,” is a natural carbamate. The preparation of DDT and DDD, which includes the cancer drug mitotane, involves electrophilic aromatic substitution and carbonium ion chemistry and illustrates ortho and para ring selectivity. Vietnam defoliants, presented alongside pesticides and herbicides, involve the syntheses of 2,4-D and 2,4,5-T, which illustrate nucleophilic aromatic substitution, benzyne generation, and dioxin formation. “Chemical Carcinogenesis” comprises the metabolism and chemistry of polycyclic aromatic hydrocarbons, benzene versus toluene, aromatic amines, azo dyes, nitrosamines, and natural carcinogens (such as aflatoxin). Protein and nucleic acid chemistry includes “Chemical Warfare,” featuring tear gas, chlorine, phosgene, mustard gas, and organophosphates (such as nerve gas) and the inhibition of acetylcholinesterase. The reaction of pepper spray exemplifies the Michael reaction with nucleic acids, as do the environmental pollutants acrylamide and acrolein.Each special topic occupies 1–3 lectures of the 30–32 course lectures. The special topics and accompanying slides are intermeshed with these conventional organic chemistry topics: alkene and alkyne electrophilic addition, nucleophilic substitution (SN1, SN2), aromatic electrophilic and nucleophilic addition, aryne formation, reductive amination, carbonyl addition and condensation, conjugate addition (Michael reaction), haloform reaction, and Diels- Alder cycloaddition.It will take some work, but it’s worth the effort.Gordon W. GribbleLebanon, New HampshireMuch has already been said about the fiasco surrounding the firing of professor Maitland Jones Jr. by New York University as the result of a student petition claiming that his organic chemistry class was too difficult. Without wishing to comment on this case myself, I am reminded of a related aspect of teaching organic chemistry that I suspect others may also have experienced.Organic chemistry seems to hold a special place in the hearts and minds of most practicing physicians. Some have been left with very positive feelings about this subject, while others have very negative feelings. Both groups of doctors keenly remember how important it was for them to receive good grades in organic chemistry to be admitted to medical school.Today, when I tell my doctor that I’ve taught organic chemistry, this always draws an immediate response. Some light up with a smile and tell me how much they’ve enjoyed this class, while others frown and offer words to the contrary. When the latter happens, this does give me pause for thought. Is this the right doctor for me? On one occasion, only moments before I was anesthetized for a colonoscopy, my gastroenterologist asked me what class I was teaching at my university. When I told her it was organic chemistry, her face lit up with a smile. Oh, what a relief that was.Steven L. RegenBethlehem, Pennsylvania CorrectionsFeb. 13, 2023, page 8: In the news story about Croda’s acquisition of Solus BioTech, the caption incorrectly labels parts of the ceramide NP structure. The sphingosine group is red and the fatty acid is blue, not the other way around.Feb. 13, 2023, page 13: The news story about Alondra Nelson misidentifies the organization she is returning to. It is the Institute for Advanced Study, not the Institute for Advanced Studies. And the institute is in Princeton, New Jersey, not part of Princeton University.

Metabolism of benzo[a]pyrene after low-dose subchronic exposure to an industrial mixture of carcinogenic polycyclic aromatic hydrocarbons in rats: a cocktail effect study.

Polycyclic aromatic hydrocarbons (PAHs) are interesting environmental pollutants for understanding cocktail effects. High-molecular-weight-PAHs (HMW-PAHs) are classified as probable or possible carcinogens; only benzo[a]pyrene (B[a]P) is a certain carcinogen in humans. Their toxicity depends on their metabolic activation. While 3-hydroxybenzo[a]pyrene (3-OHB[a]P) represents its detoxification pathway, trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (tetrol-B[a]P) represents the carcinogenicity pathway. The objective was to study the metabolism of B[a]P and HMW-PAHs during chronic low-dose exposure to B[a]P or a PAH mixture. Rats were exposed orally 5 times/week for 10weeks to low-levels of B[a]P (0.02 and 0.2mg.kg-1.d-1) or to an industrial mixture extracted from coal tar pitch (CTP) adjusted to 0.2mg.kg-1.d-1 B[a]P. Urinary levels of monohydroxy-, diol-, and tetrol-PAH were measured during weeks 1 and 10 by HPLC-fluorescence and GC‒MS/MS. After 1 week, the percentages of B[a]P eliminated as 3-OHB[a]P and tetrol-B[a]P were not different depending on the dose of B[a]P, whereas they were reduced by half in the CTP group. Repeated exposure led to an increase in the percentages of the 2 metabolites for the 0.02-B[a]P group. Moreover, the percentage of B[a]P eliminated as 3-OHB[a]P was equal in the 0.2-B[a]P and CTP groups, whereas it remained halved for tetrol-B[a]P in the CTP group. The percent elimination of HMW-PAH metabolites did not vary between weeks 1 and 10. Thus, dose, duration of exposure and chemical composition of the mixture have a major influence on PAH metabolism that goes beyond a simple additive effect. This work contributes to the reflection on determination of limit values and risk assessments in a context of poly-exposures.

Toxicokinetic analyses of naphthalene, fluorene, phenanthrene, and pyrene in humans after single oral administration

Polycyclic aromatic hydrocarbons (PAHs) are generated by incomplete combustion of organic matter. They have health effects in multiple organs and can cause lung, skin, and bladder cancers in humans. Although data regarding their toxicity is available, information on the absorption, distribution, metabolism, and excretion of PAHs in humans is very limited. In the present study, deuterium-labeled naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), and pyrene (Pyr) were orally administered as a single dose (0.02–0.04 mg/kg) to eight healthy adults. Both serum and urine samples were monitored for 72 h after the exposure. Parent compounds and PAH metabolites (monohydroxy-PAHs; OH-PAHs) were measured by headspace-solid phase microextraction coupled with gas chromatography–mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry, respectively. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment models were constructed and validated for each PAH. Subsequently, all of the parent compounds were rapidly absorbed (Tmax: 0.25 to 1.50 h) after oral administration and excreted in urine with a biological half-life (T1/2) of 1.01 to 2.99 h. The fractional urinary excretion (Fue) of OH-PAHs ranged from 0.07 % to 11.3 %; their T1/2 values ranged from 3.4 to 11.0 h. The two-compartment models successfully described the toxicokinetic characteristics of each PAH and its metabolites. Fue and the two-compartment models could be useful tools for exposure simulation or dose-reconstruction of PAHs. The results of this study will provide useful information for interpreting biomonitoring data of PAHs.

Genetic features of the marine polychaete Sirsoe methanicola from metagenomic data

The methane ice worm Sirsoe methanicola is the only marine polychaete species observed to colonize the methane hydrates of the Gulf of Mexico. Methane hydrates are ephemeral features of deep-sea cold seeps, and finding worm-colonized hydrates is rare; thus, little is known about these organisms. Recent metagenomic analysis predicted prokaryotic taxa and pathways from S. methanicola gut contents and worm fragments. Here, we increase the genetic information known about S. methanicola by assembling its nuclear rRNA genes (18S rRNA and 28S rRNA), mitochondrial genome (mitogenome), and other protein-coding genes from metagenomic data. Assembled 18S rRNA and 28S rRNA gene sequences of S. methanicola were near-identical to previously reported S. methanicola sequences. The 17,403-bp mitogenome of S. methanicola is the first mitogenome sequence of the family Hesionidae, consisting of 39.03% G+C content, 13 protein-coding genes, 24 tRNAs (including two split trnM genes), and 2 rRNA genes. Protein-coding genes in the S. methanicola metagenomes assigned to the phylum Annelida were involved in cell adhesion, signaling, ubiquitin system, metabolism, transport, and other processes. From the metagenomes, we also found 42 homologs of the cytochrome P450 (CYP) superfamily putatively involved in polycyclic aromatic hydrocarbon (PAH) metabolism. Our results encourage further studies into the genetic adaptations of S. methanicola to its methane hydrate habitat, especially in the context of deep-sea ecology and nutrient cycling.

The diversity and function of the in-situ fungal communities in response to polycyclic aromatic hydrocarbons in the urban wetland.

PAHs (polycyclic aromatic hydrocarbons) increases the potential harm to ecosystem and human health. The fungi is considered as a powerful choice for degradation of PAHs. The researches on the effect of PAHs on fungal population in sediment/soil mostly stayed in the laboratory simulation that is based on extreme pollution. This study investigated the fungal population of the urban wetland by high-throughput sequencing in-situ micro-pollution state. Our statistical analysis revealed significant difference in the whole fungal population at the phylum among three land use types in typical urban wetland. Among them, Ascomycota was the dominant fungi at the phyla in three land use types. Fungal genus of degrading PAHs were significantly correlated with Dibenz[a, h]anthracene (P = 0.018) in ditch wetland, Total Organic Carbon (P = 0.02) and Fluoranthene (P = 0.04) in riverine wetland, and ElectricalConductivity (P = 0.018) in agricultural land. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) suggested that 20 enzymes were present related to PAHs metabolism in three land use types. Specifically, monoxygenase, dehydrogenase, and laccase were most abundant among inferred enzymes, indicating that the urban wetland had potential for the degradation of PAHs. This study contributed to in-depth understanding of the structure and function of fungal population and provided a theoretical basis for PAHs microbial remediation in the in-situ environment.

Nitrogen transformation promotes the anaerobic degradation of PAHs in water level fluctuation zone of the Three Gorges Reservoir in Yangtze River, China: Evidences derived from in-situ experiment

Polycyclic aromatic hydrocarbons (PAHs) pose a great threat to human health and ecological system safety. The interception of nitrogen is common found in the riparian zone. However, there is no evidence on how nitrogen addition affects the anaerobic degradation of PAHs in soil of the water-level-fluctuation zone (WLFZ) of the Three Gorges Reservoir (TGR) in Yangtze River, China. Here, we investigated the PAHs degradation rate, the variation of key functional genes and microbial communities after nitrogen addition in soil that experienced a flooding period of water-level-fluctuation. The results revealed that the ∑16PAHs were decreased 16.19 %–36.65 % and more 3–5-rings PAHs were biodegraded with nitrogen addition in WLFZ. The most genes involved in PAHs-anaerobic degradation and denitrification were up-regulated by nitrate addition, and phyla Firmicutes, Actinobacteria and Proteobacteria were more advantages in nitrogen addition groups. The Tax4Fun based genome function analysis revealed that the microbial activity of PAHs-degradation increased with nitrate addition. The co-occurrence network analysis indicated that nitrogen addition accelerated the metabolism of nitrogen and PAHs. It is the first time to provide the direct experimental evidences that nitrogen transformation in the WLFZ soil promotes anaerobic PAHs degradation. This work is of importance to understand the effect of nitrogen intercepted in the WLFZ soil of TGR in Yangtze River, China.