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Synergistic Effects of Prebiotics and Antineoplastic Drug Induced Immune Cell Activation and Lymphoma Inhibition in Modeled Microgravit

Posted on:2018-06-04Degree:Ph.DType:Dissertation
University:Texas Southern UniversityCandidate:Mansoor, ElvedinaFull Text:PDF
GTID:1474390020456408Subject:Environmental Science
Abstract/Summary:
According to the numerous research articles, constant influence of weightlessness (microgravity) leads to modifications of many physiological cellular processes such as: proliferation, early activation and differentiation, signal transduction, cytoskeletal architecture, and gene expression. We investigated two different cell lines: Human Peripheral Mononuclear Cells (PBMC's) and cancer of Lymphoma (Ramos cells) grown in two culture environments; modeled microgravity (MMG) using High Aspect Ratio Vessels (HARV's) and normal condition (1g) using T-Flasks.;The first part of the experiment included exposure to Active Hexose Correlated Compound (AHCC); nutritional supplement used as a countermeasure to boost immune system in response to the stressor; modeled microgravity and Ionomycin (ionophore) used to measure intracellular levels of calcium. AHCC concentrations (0, 50, 250 and 500 microg/ml) and Ionomycin (2microl/ml) were used to treat cells and assess changes at 0, 24, 48 and 72 hours.;The second part of experiment included treatment with Cyclophosphamide; an extensive antineoplastic agent used with Ramos cells and activated by S9 Liver microsomes, to investigate the metabolic response of tumor cells at 1g and MMG over the 72 hours' period. Cell counts and MTT assay were selected to study cytotoxicity and effects within cellular cultures within their corresponding environments (1g or MMG).;Exposure to modeled microgravity (MMG) and 1g environment for 72 hours following conclusions were made: alteration of cells when treated with AHCC in modeled microgravity show that AHCC induces increase in PBMC's proliferation, calcium release is not favored, downmodulation of F-actin, and cytokine production showed the effect of AHCC as an anti-inflammatory compound to inhibit a continuous production of different cytokines. For the second part of experiment, cyclophosphamide activated with S9 microsomes showed a 100% cell death as early as 24 hours' post treatment in MMG. Combination of activated cyclophosphamide with the different concentrations of AHCC showed cytotoxic effect at 72 hours compared to the earlier time points. Inactivated cyclophosphamide was also able to induce cytotoxicity as early as 24 hours in MMG. Finally, based on our findings microgravity might have a possible potentiating effect on both activated and inactivated cyclophosphamide alone and in combination with AHCC, as the cytotoxic effects under this condition was more significant than in 1G.
Keywords/Search Tags:AHCC, Cell, Effects, Modeled, MMG, Microgravity, Cyclophosphamide
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