Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity.

The metabolism of two of benzene's phenolic metabolites, phenol and hydroquinone, by peroxidase enzymes has been studied in detail. Studies employing horseradish peroxidase and human myeloperoxidase have shown that in the presence of hydrogen peroxide phenol is converted to 4,4'-diphenoquinone and other covalent binding metabolites, whereas hydroquinone is converted solely to 1,4-benzoquinone. Surprisingly, phenol stimulates the latter conversion rather than inhibiting it, an effect that may play a role in the in vivo myelotoxicity of benzene. Indeed, repeated coadministration of phenol and hydroquinone to B6C3F1 mice results in a dramatic and significant decrease in bone marrow cellularity similar to that observed following benzene exposure. A mechanism of benzene-induced myelotoxicity is therefore proposed in which the accumulation and interaction of phenol and hydroquinone in the bone marrow and the peroxidase-dependent formation of 1,4-benzoquinone are important components. This mechanism may also be responsible, at least in part, for benzene's genotoxic effects, as 1,4-benzoquinone has been shown to damage DNA and is shown here to induce multiple micronuclei in human lymphocytes. Secondary activation of benzene's phenol metabolites in the bone marrow may therefore play an important role in benzene's myelotoxic and carcinogenic effects

Laboratory phenomics predicts field performance and identifies superior indica haplotypes for early seedling vigour in dry direct-seeded rice

Seedling vigour is an important agronomic trait and is gaining attention in Asian rice (Oryza sativa) as cultivation practices shift from transplanting to forms of direct seeding. To understand the genetic control of rice seedling vigour in dry direct seeded (aerobic) conditions we measured multiple seedling traits in 684 accessions from the 3000 Rice Genomes (3K-RG) population in both the laboratory and field at three planting depths. Our data show that phenotyping of mesocotyl length in laboratory conditions is a good predictor of field performance. By performing a genome wide association study, we found that the main QTL for mesocotyl length, percentage seedling emergence and shoot biomass are co-located on the short arm of chromosome 7. We show that haplotypes in the indica subgroup from this region can be used to predict the seedling vigour of 3K-RG accessions. The selected accessions may serve as potential donors in genomics-assisted breeding programs

Ketocarotenoid production in tomato triggers metabolic reprogramming and cellular adaptation: The quest for homeostasis

Plants are sessile and therefore have developed an extraordinary capacity to adapt to external signals. Here, the focus is on the plasticity of the plant cell to respond to new intracellular cues. Ketocarotenoids are high-value natural red pigments with potent antioxidant activity. In the present study, system-level analyses have revealed that the heterologous biosynthesis of ketocarotenoids in tomato initiated a series of cellular and metabolic mechanisms to cope with the formation of metabolites that are non-endogenous to the plant. The broad multilevel changes were linked to, among others, (i) the remodelling of the plastidial membrane, where the synthesis and storage of ketocarotenoids occurs; (ii) the recruiting of core metabolic pathways for the generation of metabolite precursors and energy; and (iii) redox control. The involvement of the metabolites as regulators of cellular processes shown here reinforces their pivotal role suggested in the remodelled ‘central dogma’ concept. Furthermore, the role of metabolic reprogramming to ensure cellular homeostasis is propose

Self-Regulation in a Web-Based Course: A Case Study

Little is known about how successful students in Web-based courses self-regulate their learning. This descriptive case study used a social cognitive model of self-regulated learning (SRL) to investigate how six graduate students used and adapted traditional SRL strategies to complete tasks and cope with challenges in a Web-based technology course; it also explored motivational and environmental influences on strategy use. Primary data sources were three transcribed interviews with each of the students over the course of the semester, a transcribed interview with the course instructor, and the students’ reflective journals. Archived course documents, including transcripts of threaded discussions and student Web pages, were secondary data sources. Content analysis of the data indicated that these students used many traditional SRL strategies, but they also adapted planning, organization, environmental structuring, help seeking, monitoring, record keeping, and self-reflection strategies in ways that were unique to the Web-based learning environment. The data also suggested that important motivational influences on SRL strategy use—self-efficacy, goal orientation, interest, and attributions—were shaped largely by student successes in managing the technical and social environment of the course. Important environmental influences on SRL strategy use included instructor support, peer support, and course design. Implications for online course instructors and designers, and suggestions for future research are offered

The benzene metabolite para-benzoquinone is genotoxic in human, phorbol-12-acetate-13-myristate induced, peripheral blood mononuclear cells at low concentrations

Benzene is one of the most prominent occupational and environmental pollutants. The substance is a proven human carcinogen that induces hematologic malignancies in humans, probably at even low doses. Yet knowledge of the mechanisms leading to benzene-induced carcinogenesis is still incomplete. Benzene itself is not genotoxic. The generation of carcinogenic metabolites involves the production of oxidized intermediates such as catechol, hydroquinone and para-benzoquinone (p-BQ) in the liver. Further activation to the ultimate carcinogenic intermediates is most probably catalyzed by myeloperoxidase (MPO). Yet the products of the MPO pathway have not been identified. If an oxidized benzene metabolite such as p-BQ was actually the precursor for the ultimate carcinogenic benzene metabolite and further activation proceeds via MPO mediated reactions, it should be possible to activate p-BQ to a genotoxic compound in vitro. We tested this hypothesis with phorbol-12-acetate-13-myristate (PMA) activated peripheral blood cells exposed to p-BQ, using the cytokinesis-block micronucleus test. Addition of 20–28 ng/ml PMA caused a significant increase of micronuclei at low and non-cytotoxic p-BQ concentrations between 0.04 and 0.2 μg/ml (0.37–1.85 μM). Thus with PMA or p-BQ alone no reproducible elevation of micronuclei was seen up to toxic concentrations. PMA and p-BQ induce micronuclei when administered jointly. Our results add further support to the hypothesis that MPO is a key enzyme in the activation of benzene

Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase.

Macrophages, an important cell-type of the bone marrow stroma, are possible targets of benzene toxicity because they contain relatively large amounts of prostaglandin H synthase (PHS), which is capable of metabolizing phenolic compounds to reactive species. PHS also catalyzes the production of prostaglandins, negative regulators of myelopoiesis. Studies indicate that the phenolic metabolites of benzene are oxidized in bone marrow to reactive products via peroxidases. With respect to macrophages, PHS peroxidase is implicated, as in vivo benzene-induced myelotoxicity is prevented by low doses of nonsteroidal anti-inflammatory agents, drugs that inhibit PHS. Incubations of either 14C-phenol or 14C-hydroquinone with a lysate of macrophages collected from mouse peritoneum (greater than 95% macrophages), resulted in an irreversible binding to protein that was dependent upon H2O2, incubation time, and concentration of radiolabel. Production of protein-bound metabolites from phenol or hydroquinone was inhibited by the peroxidase inhibitor aminotriazole. Protein binding from 14C-phenol also was inhibited by 8 microM hydroquinone, whereas binding from 14C-hydroquinone was stimulated by 5 mM phenol. The nucleophile cysteine inhibited protein binding of both phenol and hydroquinone and increased the formation of radiolabeled water-soluble metabolites. Similar to the macrophage lysate, purified PHS also catalyzed the conversion of phenol to metabolites that bound to protein and DNA; this activation was both H2O2- and arachidonic acid-dependent. These results indicate a role for macrophage peroxidase, possibly PHS peroxidase, in the conversion of phenol and hydroquinone to reactive metabolites and suggest that the macrophage should be considered when assessing the hematopoietic toxicity of benzene

Fatty acids in arbuscular mycorrhizal fungi are synthesized by the host plant

Plants form beneficial associations with arbuscular mycorrhizal fungi, which facilitate nutrient acquisition from the soil. In return, the fungi receive organic carbon from the plants. The transcription factor RAM1 (REQUIRED FOR ARBUSCULAR MYCORRHIZATION 1) is crucial for this symbiosis, and we demonstrate that it is required and sufficient for the induction of a lipid biosynthetic pathway that is expressed in plant cells accommodating fungal arbuscules. Lipids are transferred from the plant to mycorrhizal fungi, which are fatty acid auxotrophs, and this lipid export requires the glycerol-3-phosphate acyltransferase RAM2, a direct target of RAM1. Our work shows that in addition to sugars, lipids are a major source of organic carbon delivered to the fungus, and this is necessary for the production of fungal lipids

Investigation of sp carbon chain interaction with silver nanoparticles by Surface Enhanced Raman Scattering

Surface Enhanced Raman Spectroscopy (SERS) is exploited here to investigate the interaction of isolated sp carbon chains (polyynes) in a methanol solution with silver nanoparticles. Hydrogen-terminated polyynes show a strong interaction with silver colloids used as the SERS active medium revealing a chemical SERS effect. SERS spectra after mixing polyynes with silver colloids show a noticeable time evolution. Experimental results, supported by density functional theory (DFT) calculations of the Raman modes, allow us to investigate the behavior and stability of polyynes of different lengths and the overall sp conversion towards sp2 phase.Comment: 19 pages, 7 figures, 1 table