This work was dedicated to quantify and distinguish the radio- and chemitoxic effects of environmentally relevant low doses of uranium on the metabolism of microorganisms and multicellular organisms by a modern and highly sensitive microcalorimetry. In such low-dose regime, lethality is low or absent. Therefore, quantitative assays based on survival curves cannot be employed, particularly for multicellular organisms. Even in the case of microbial growth, where individual cells may be killed by particle radiation, classical toxicity assessments based on colony counting are not only extremely time-consuming but also highly error-prone.
Therefore, measuring the metabolic activity of the organism under such kinds of conditions would give an extremely valuable quantitative measure of viability that is based on life cell monitoring, rather than determining lethality at higher doses and extrapolating it to the low dose regime. The basic concept is simple as it relies on the metabolic heat produced by an organism during development, growth or replication as an inevitable byproduct of all biochemical processes. A metabolic effect in this concept is defined as a change in heat production over time in the presence of a stressor, such as a heavy metal. This approach appeared to be particular versatile for the low dose regime. Thus, the thesis attempted in this case to measure the enthalpy production of a bacterial population as a whole to derive novel toxicity concepts.
In the following chapters, an introduction about the properties of ionizing radiation will be briefly presented, in addition to a review about the isothermal calorimetry and its application in studying the bacterial growth. Later in chapter 2, the effect of uranium on the metabolic activity of three different bacterial strains isolated form a uranium mining waste pile together with a reference strain that is genetically related to them will be investigated. Due to the lack of published dedicated calibration techniques for the interpretation of heat production of bacterial cells under the conditions of calorimetric recordings, additional experiments, thorough investigations of the effects of experimental conditions, have been carried out in order to guide the interpretation of calorimetric results.
In chapter 3, the differentiation between chemi- and radiotoxicity of uranium has been addressed by isotope exchange, which was a key effort in this thesis as it opens new experimental approaches in radioecology. In chapter 4, through investigating the role of the tripeptide glutathione (GSH) in detoxifying uranium, it will be shown to which degree the intrinsically unspecific signal provided by metabolic heat can be related to highly specific metabolic pathways of an organism, when combined with genetic engineering. The demonstration of gaining molecule-specific information by life metabolic monitoring was another experimental challenge of this thesis and provides proof of principle that can be extended to many organisms.
Finally in chapter 5, an attempt has been undertaken to establish a minimal food chain, in order to study the effects of the exposure of a multicellular organism to uranium through its diet.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:29184 |
| Date | 11 January 2016 |
| Creators | Obeid, Muhammad Hassan |
| Contributors | Stumpf, Thorsten, Fahmy, Karim, Bernhard, Gert, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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