ETD Collection

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Has files: YesSubject: search.filters.subject.Genetic toxicology.

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    Genotoxicity of mycotoxins in an improved drosophila wing spot test and other short-term effects
    (1992) Pacella, Rosana Elizabeth
    Attempts have been made recently to improve the Drosophiia Somatic Mutation and Recombination wing spot test (SMART) by inciudjig insecticide resistance genes that confer high bioactivation (HB) to SMART tester strains. A drawback of the HB lines is the presence of whorling of wing hairs which interferes with scoring for mutant spots. The gene responsible for this whorling effect, which I have named paisley (ply), was shown to be recessive and located around position 90 on chromosome 2 and is thus linked to the RI gene responsible for the high constitutive expression of cytochrome P450- dependent activities typical of HB strains. (Abbreviation abstract)
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    Temporal expression of Dmp53 and SNAMA isoforms and their relation to genotoxic stress.
    (2015) Nweke, Ekene Emmanuel
    RBBP6 is an E3 Ubiquitin ligase protein with a U-box motif. It interacts with p53 and Rb and is linked to several cellular functions. SNAMA is the Drosophila RBBP6 homolog, but is less characterized than its vertebrate counterparts. Gene expression studies on Drosophila have a potential to advance the knowledge on molecular mechanism underlying genotoxic stress. Previous studies have shown that SNAMA plays a critical role as an apoptosis suppressor and possibly in responses to genotoxic stress. The molecular basis for this is, however, unknown. Initially, two isoforms were identified by bioinformatics and one (Snama A) experimentally as well. Here, we confirm experimentally the existence of the second isoform (Snama B). We also show that these are differentially expressed during development and when the organism undergoes genotoxic stress. Total RNA samples were used to demonstrate gene expression by using Reverse Transcriptase Polymerase Chain Reaction. Using samples collected at different stages of development and from adult flies treated with the DNA damaging agent, irinotecan, it is shown that these isoforms are differentially expressed throughout development and upon genotoxic stress. This knowledge may help to understand the functional role SNAMA plays in normal physiology and in response to genotoxic stress. Furthermore, the results show that SNAMA is involved in a potentially beneficial intervention whereby the glycolytic pathway is bypassed by the addition of methyl pyruvate.
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    Stress response to genotoxic agents and to infection
    (2012-10-08) Hull, Rodney
    Insects have evolved various physiological responses to cope with stressors such as pathogens, toxins and environmental factors. It is known that the responses resulting from infection or DNA damage share some of the same pathways. Exposure of Drosophila melanogaster and the dung beetle Euoniticellus intermedius to stress led to changes in the expression of proteins involved in metabolism, development, protein degradation, mRNA processing and stress responses. Stress responses in D. melanogaster are well characterised. However, the role played by Drosophila p53 (Dmp53) and a member of the retinoblastoma binding protein 6 (RBBP6) family, Snama, are unknown. Snama has been proposed to play a role in Dmp53 regulation. Following DNA damage we investigated the role of Dmp53 and Snama. Flies recovering from camptothecin treatment display a glycolytic flux, involving a metabolic shift, different to that observed in cancer cells. Camptothecin treatment leads to an increase in the mortality of both sexes. Furthermore, females show a specific decrease in fecundity which is due to an increase in Dmp53 dependent apoptosis in the ovaries and is accompanied by a depletion of Snama and an increase in Dmp53 transcripts. Expression data indicated that Dmp53 activity may be largely regulated at the protein level. Bypassing glycolysis through methyl pyruvate supplementation led to differential expression of Dmp53 and Snama and improved reproduction and embryonic development. These results highlight differences between the metabolic strategies used by cancerous and non-cancerous cells which may be exploited in future chemotherapies. While immune responses amongst insect orders are evolutionarily conserved, many remain uncharacterised. To investigate the immune system of an organism that lives in a microbe rich environment, E. intermedius was infected with the fungal pathogen Beauveria bassiana. This resulted in decreased lifespan and fecundity. Homologs of proteins involved in the immune response of insects were identified in E. intermedius, including a member of the Toll family of proteins, an insect defensin (present in the hemolymph) as well as a homolog of the serine protease Persephone. These results show that immune signalling pathways are conserved in this dung beetle.