Vaping: Cell Damage at the Receiving ENDS.
Ontology highlight
ABSTRACT:
SUBMITTER: Knapp S
PROVIDER: S-EPMC7462343 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC7781006 | biostudies-literature
Project description:BackgroundAlthough the harm to health from electronic nicotine delivery systems (ENDS) compared to smoked tobacco remains highly uncertain, society and governments still need to know the likely range of the relative harm to inform regulatory policies for ENDS and smoking.MethodsWe identified biomarkers with specificity of association with different disease groupings e.g., volatile organic compound (VOCs) for chronic obstructive pulmonary disease; and tobacco-specific N´-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for all cancers. We conducted a review of recent studies (post January 2017) that compared these biomarkers between people exclusively using ENDS and those exclusively smoking tobacco. The percentage differences in these biomarkers, weighted by study size and adjusted for acrolein from other sources, were used as a proxy for the assumed percentage difference in disease harm between ENDS and smoking. These relative differences were applied to previously modelled estimates of smoking-related health loss (in health-adjusted life-years; HALYs).ResultsThe respective relative biomarker levels (ENDS vs smoking) were: 28% for respiratory diseases (five results, three studies); 42% for cancers (five results, four studies); and 35% for cardiovascular (seven results, four studies). When integrated with the HALY impacts by disease, the overall harm to health from ENDS was estimated to be 33% that of smoking.ConclusionsThis analysis, suggests that the use of modern ENDS devices (vaping) could be a third as harmful to health as smoking in a high-income country setting. But this estimate is based on a limited number of biomarker studies and is best be considered a likely upper level of ENDS risk given potential biases in our method (i.e., the biomarkers used being correlated with more unaccounted for toxicants in smoking compared to with using ENDS).
| S-EPMC8577029 | biostudies-literature
Project description:We discovered that the cell-free chromatin assembly system senses free DNA ends and mounts a DNA double-strand break response. DNA ends are first recognized by the Ku complex and later resected. The phosphorylation of H2A.V (homologous to gH2A.X) initiates at DNA breaks and spreads over ten thousands of base pairs of DNA within a few minutes. The phosphorylation of gH2A.V remains tightly associated with the damaged DNA in cis and does not transfer to intact DNA circles in the same reaction. Our descriptions of the damage-related proteome and phospho-proteome provide a rich resource for in-depth mechanistic analyses of the DNA chromosome break response in this model system.
2019-07-22 | GSE126415 | GEO
Project description:Mammalian cells require non-homologous end joining (NHEJ) for the efficient repair of chromosomal DNA double-strand breaks. A key feature of biological sources of strand breaks is associated nucleotide damage, including base loss (abasic or apurinic/apyrimidinic (AP) sites). At single-strand breaks, 5'-terminal abasic sites are excised by the 5'-deoxyribose-5-phosphate (5'-dRP) lyase activity of DNA polymerase beta (pol beta): here we show, in vitro and in cells, that accurate and efficient repair by NHEJ of double-strand breaks with such damage similarly requires 5'-dRP/AP lyase activity. Classically defined NHEJ is moreover uniquely effective at coupling this end-cleaning step to joining in cells, helping to distinguish this pathway from otherwise robust alternative NHEJ pathways. The NHEJ factor Ku can be identified as an effective 5'-dRP/AP lyase. In a similar manner to other lyases, Ku nicks DNA 3' of an abasic site by a mechanism involving a Schiff-base covalent intermediate with the abasic site. We show by using cell extracts that Ku is essential for the efficient removal of AP sites near double-strand breaks and, consistent with this result, that joining of such breaks is specifically decreased in cells complemented with a lyase-attenuated Ku mutant. Ku had previously been presumed only to recognize ends and recruit other factors that process ends; our data support an unexpected direct role for Ku in end-processing steps as well.
| S-EPMC2859099 | biostudies-literature
Project description:Study objectivesTo compare the prices paid for nicotine vaping products (NVPs) and supplies among current NVP users to prices paid for cigarettes among current smokers.DataThe 2016 International Tobacco Control Four Country Vaping and Smoking Survey (4CV1). Key measures included: (1) self-reported prices paid for reusable NVPs (eg, rechargeable devices with cartridges and tank system devices with e-liquids) in the 3-month period prior to the survey among current NVP users, (2) prices paid for disposable NVPs, cartridges and e-liquids purchased in the last 30 days among current NVP users and (3) self-reported prices paid for cigarettes among current smokers.ResultsDisposable NVP price was higher than the price of a comparable unit for combustible cigarettes in England (EN), USA and Canada (CA). Prefilled cartridge price was higher than the price of a comparable unit of cigarettes in USA and CA, but lower in EN and Australia. E-liquid price was consistently lower than the price of a comparable unit of cigarettes across four countries. For start-up costs, price of a rechargeable device is approximately 3-5 times higher than a pack of cigarettes in four countries.ConclusionNVP prices were generally higher than prices of combustible cigarettes, especially the high upfront NVP devices. The high upfront costs of purchasing a reusable NVP may discourage some smokers from switching to vaping. However, the average lower costs of cartridges and e-liquids relative to a package of cigarettes make switching to a NVP an attractive alternative to smoking in the long term so long as smokers switch completely to vaping.
| S-EPMC7507861 | biostudies-literature
Project description:BackgroundThe use of electronic nicotine delivery systems (ENDS), also known as vaping, is becoming popular among young adults. Few studies have explored the psychological factors that predict ENDS use and susceptibility in young adults, in addition to known demographic predictors.MethodIn a cross-sectional survey design, 521 young adults (37% male), ages 18-25 from the United States, were recruited via Amazon's Mechanical Turk (MTurk) in 2019, to answer an online survey measuring demographic characteristics and psychological characteristics related to mental health and the Big Five personality traits. The survey also included measures of ENDS ever-use, current use, and susceptibility (never users open to trying ENDS), which we predicted from the demographic and psychological measures using independent and multiple binary logistic regression analyses.ResultsOf those surveyed (n = 521), 282 (54.1%) were ENDS ever-users, 93 (17.9%) were current ENDS users, and 61 (11.7%) were ENDS susceptible; 62 (11.9%) were current smokers. Demographically, young adults lower in adulthood socioeconomic-status (SES), not pursuing education further than high school, and current smokers were more likely to be ENDS users. Psychologically, young adults higher in anxiety and lower in conscientiousness more likely to have ever-used ENDS. Lower conscientiousness further predicted current ENDS use and ENDS susceptibility.ConclusionIn this sample of MTurk workers, young adults with experience in vaping were more demographically and psychologically vulnerable than young adults with no experience in vaping. Young adults interested in vaping, but without prior experience, were less conscientious than their non-interested peers. Interventions to target vaping use should focus on economically disadvantaged young adults and those lower in conscientiousness.
| S-EPMC8415821 | biostudies-literature
Project description:The V(D)J recombinase catalyzes DNA transposition and translocation both in vitro and in vivo. Because lymphoid malignancies contain chromosomal translocations involving antigen receptor and protooncogene loci, it is critical to understand the types of "mistakes" made by the recombinase. Using a newly devised assay, we characterized 48 unique TCRbeta recombination signal sequence (RSS) end insertions in murine thymocyte and splenocyte genomic DNA samples. Nearly half of these events targeted "cryptic" RSS-like elements. In no instance did we detect target-site duplications, which is a hallmark of recombinase-mediated transposition in vitro. Rather, these insertions were most likely caused by either V(D)J recombination between a bona fide RSS and a cryptic RSS or the insertion of signal circles into chromosomal loci via a V(D)J recombination-like mechanism. Although wild-type, p53, p53 x scid, H2Ax, and ATM mutant thymocytes all showed similar levels of RSS end insertions, core-RAG2 mutant thymocytes showed a sevenfold greater frequency of such events. Thus, the noncore domain of RAG2 serves to limit the extent to which the integrity of the genome is threatened by mistargeting of V(D)J recombination.
| S-EPMC2118463 | biostudies-literature
Project description:With the increase of atmospheric oxygen 2.3 billion years ago, mechanisms evolved to mitigate the toxic effects of oxygen radicals. Telomeres appear particularly susceptible to oxidative damage, which leads to cellular and organismal aging, cancer, cardiac failure and other diseases. Specific mechanisms of telomere protection from oxidative damage and the molecular consequences of the damage have not been described. Here, we identify the antioxidant enzyme peroxiredoxin 1 (PRDX1) enriched in telomeric chromatin in S and G2 phases of the cell cycle during which telomeres become replicated. PRDX1 depletion leads to oxidative damage of telomeric DNA without affecting the bulk of genomic DNA. The oxidized nucleotide 8-oxo-2’deoxyguanosine-5’-triphosphate (8oxodGTP) can be incorporated by telomerase into telomeric repeats but it mediates premature chain termination when incorporated as first G in the telomeric 5’-TTAGGG-3’ sequence. In dependency of the alignment position within the telomerase RNA template, terminus 8oxoG containing DNA substrates also completely block extension by telomerase. We propose two major mechanisms by which PRDX1 counteracts telomere damage and aging. In safeguarding telomeres from oxygen radicals, PRDX1 prevents DNA damage, telomere replication defects and mutations that will perturb recognition of telomeric DNA by shelterin components. In preventing modification of the telomeric DNA substrate and the dNTP pool, PRDX1 preserves telomeres for elongation by telomerase.
2016-12-07 | PXD002626 | Pride
Project description:Cytokinesis in Trypanosoma brucei, an early branching protozoan, occurs along its longitudinal axis uni-directionally from the anterior tip of the new flagellum attachment zone filament toward the cell's posterior end. However, the underlying mechanisms remain elusive. Here we report that cytokinesis in T. brucei is regulated by a concerted action of Polo-like kinase, Aurora B kinase, and a trypanosome-specific protein CIF1. Phosphorylation of CIF1 by Polo-like kinase targets it to the anterior tip of the new flagellum attachment zone filament, where it subsequently recruits Aurora B kinase to initiate cytokinesis. Consistent with its role, CIF1 depletion inhibits cytokinesis initiation from the anterior end of the cell, but, surprisingly, triggers cytokinesis initiation from the posterior end of the cell, suggesting the activation of an alternative cytokinesis from the opposite cell end. Our results reveal the mechanistic roles of CIF1 and Polo-like kinase in cytokinesis initiation and elucidate the mechanism underlying the recruitment of Aurora B kinase to the cytokinesis initiation site at late anaphase. These findings also delineate a signaling cascade controlling cytokinesis initiation from the anterior end of the cell and uncover a backup cytokinesis that is initiated from the posterior end of the cell when the typical anterior-to-posterior cytokinesis is compromised.
| S-EPMC4812729 | biostudies-literature
Project description: Not available
| S-EPMC6670025 | biostudies-literature