Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 19 of 19 for “"genotoxins"”.
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Molecular mechanism of interactions between estrogen receptor and estrogen receptor selective genotoxins
Although one million new breast cancer cases arise each year worldwide, therapies to treat the disease are limited. Conventional treatments including the chemotherapeutic agent, Tamoxifen, have had only limited success, often showing uncomfortable side effects. Our group has proposed a new scheme …
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Novel genotoxins that target estrogen receptor- and androgen receptor- positive cancers : identification of DNA adducts, pharmacokinetics, and mechanism
We have designed and synthesized novel molecules capable of selectively killing tumor cells that aberrantly express steroid hormone receptors. Many human breast cancers express high levels of the estrogen receptor (ER), and most prostate cancers express the androgen receptor (AR). We reasoned that …
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In vitro studies on genotoxicity and gene expression in spermatogenic cells: mechanisms and assay development
… spermatogonia, spermatocytes and spermatids. The genotoxins H2O2, doxorubicin, N-ethyl-N-nitrosourea, N-methyl-N-nitrosourea, 6-mercaptopurine, 5-bromodeoxyuridine, methyl methanesulphonate and ethyl methanesulphonate were investigated. Cells were cultured and treated with different concentrations …
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XRCC1 & DNA MTases : direct and indirect modulation of inflammation-induced DNA damage
… of genomic instability, following exposure to genotoxins. Here, we exploited cell lines engineered to carry deficiencies in BER to study repair of DNA damage induced by RONs. Toxicity and BER-intermediate levels were evaluated in XRCC1 proficient and deficient cells, following exposure to the …
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Quantifying the pro- and antimutagenic roles of DNA damage and repair
… 50 DNA repair deficient genetic backgrounds, 12 genotoxins and nearly 200 combinations thereof, I characterise the mutational spectra and genomic features of a range of DNA repair deficiencies, and describe the mutational signatures of genotoxins across multiple genetic backgrounds. Importantly, …
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Advancing Toxicology-Based Cancer Risk Assessment with Informatics
… when assessing risk including: (1) mixtures of genotoxins, (2) genotoxic metabolites, and (3) nongenotoxic carcinogens. An in silico model was developed to predict the cancer risk of a genotoxin which improved methodology for a single compound and mixtures. Monte Carlo simulations performed with …
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Genotoxic effects of oestrogens and nano-NSAIDs: Genotoxic effects of oestrogens in vivo and nano- and bulk forms of NSAIDs on blood samples from prostate cancer patients
… it is known that the sensitivity of DNA to genotoxins can be heightened in patients with cancer. Patients’ and volunteers’ blood was cultured with either the bulk or nano-forms for 44 hours at 37°C, 5% CO2. Data were obtained for the Comet assay as above and the number of binucleated cells …
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Identification of MMS22 as a regulator of DNA repair
… or MMS22 are hypersensitive to a wide variety of genotoxins that stall or block replication forks, and are severely defective in their ability to recover from DNA alkylation damage. Homologous recombination (HR) is an important mechanism for the rescue of stalled or blocked replication forks and …
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Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response
… for such a response is to ensure aversion to genotoxins in food.
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Deformability and Dynamics in Linear and Looped/Supercoiled DNA with Implications for Damage Sensing
… lesions from UV-light and other environmental genotoxins and initiates nucleotide excision repair; 2) MutS, which recognizes single mismatches or unpaired nucleotides introduced during replication and initiates mismatch repair. Using linear DNA with 3-bp mismatches as mock lesions for Rad4, we …
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Uncovering vital molecular contacts within the replisome and characterizing fail-safe mechanisms ensuring genomic stability in E. coli.
… cells; however, in the presence of various genotoxins, the absence of Rep results in an increase in ssDNA gaps due to DNA damage-linked replisome decoupling. By characterizing decoupling consequences within the E. coli replisome, we have gained a deeper, more comprehensive understanding of …
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Engineering a comet-based platform for specific, sensitive, and high throughput assessment of multiple DNA repair pathways in humans
Human exposure to dangerous genotoxins is unavoidable, as DNA damaging agents are ubiquitous both in our environment and within our cells. The diversity in lesions induced by these agents led to the evolution of several DNA repair pathways that suppress the mutagenic and toxic effects of DNA …
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Disabling the intrinsic resistome of Mycobacterium tuberculosis: elucidating hierarchies of DNA repair and mutagenesis that undermine current antibiotic efficacy
… essential repair pathways under treatment with genotoxins of different mechanistic classes. To this end, the DNA crosslinking agent, mitomycin C (MMC), and the gyrase inhibitor and clinically relevant TB drug, moxifloxacin (MOX), were used. The goal was to reveal potential targets for co-drugs …
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Cellular interactions of the cytolethal distending toxins
… all CDTs are generally considered to function as genotoxins, the extent of similarity and differences within the members of the CDT-family in their cellular intoxication properties, and the molecular components of host cellular machinery that plays a role in CDT-mediated intoxication, are poorly …
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Investigating the Role of Reactive Aldehydes in the Development of Head and Neck Squamous Cell Carcinoma in Fanconi Anemia
… FA DNA repair pathway and the impact of these genotoxins (i.e., formaldehyde and acetaldehyde) on the genome. Oral keratinocytes were compared to epidermal keratinocytes because there is not a high incidence of epidermal squamous cell carcinoma reported in FA patients. I found that endogenous …
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Role of Mitochondrial Dynamics and Autophagy in Removal of Helix-Distorting Mitochondrial DNA Damage
… high levels in mtDNA by important environmental genotoxins including polycyclic aromatic hydrocarbons, ultraviolet C radiation (UVC) and mycotoxins. These lesions are irreparable and persistent in the short term, but their long-term fate is unknown. Degradation of mitochondria and mtDNA is …
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Investigating a novel small molecule inhibitor of nuclear import as an anti-cancer approach
… cancer cell survival when challenged with genotoxins such as CDDP. Using the cervical cancer model, we demonstrated that INI-43 enhanced CDDP-induced cell death synergistically, and that the enhanced cell death is mediated through stabilizing p53 protein. This associated with decreased …
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DNA damage and nutrient status as risk factors for mild cognitive impairment and Alzheimer’s disease
… in cells exposed to endogenous or exogenous genotoxins or under conditions of micronutrient deficiency. Findings from the in vitro study showed that (i) extracellular Aβ40 is not genotoxic or cytotoxic, (ii) extracellular Aβ42 reduces nuclear division capacity and induces significantly …
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Using Mouse Models to Define How The P53 R72P Polymorphism Impacts The Adverse Effects of Doxorubicin and Ionizing Radiation
<p>The single nucleotide polymorphism (SNP) at codon 72 of the tumor suppressor gene <em>p53 </em>codes for either an arginine (R) or proline (P) (p53 R72P). This SNP may impact how cells respond to genotoxic insult. Studies in cell culture and in tissues from mouse models of the SNP indicate that, …