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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The Mutagenicity, metabolism and macromolecule binding of the nitrated polycyclic aromatic hydrocarbon 3-nitroperylene / The Mutagenicity and metabolism of 3-nitroperylene

Anderson, Gregory 09 1900 (has links)
In recent years the nitrated polycyclic aromatic hydrocarbons (nitroPAH's) have been recognized as powerful mutagens in the Ames Salmonella test. Most nitroPAH’s are direct-acting mutagens in the Ames test i.e. they induce mutation in the absence of S9, and appear to be activated through nitroreduction by bacterial enzymes. Others, however, such as 3-nitroperylene, are indirect-acting mutagens and show maximum activity only when S9 is present. Studies using the Ames test have indicated that the cytochrome P-450-dependent mixed function oxidase system of S9 is responsible for the activation of 3-nitroperylene to mutagenic species. However, the pattern of P-450 isozymes involved in this process appears to be different from that involved in the conversion of most PAH's, such as the standard indirect-acting mutagen benzo(a)pyrene (B(a)P), to proximate mutagens. 6-NitroB(a)P, in contrast, behaves in an analogous manner to its parent hydrocarbon. Using appropriate Salmonella mutants, the activation of 3-nitroperylene was found to require bacterial involvement, although the nature of the bacterial contribution has yet to be determined. Studies with other mutants have indicated that nitroreduction, at least as a primary activation step, does not appear to be important. Incubation of 3-nitroperylene with high concentrations of S9 led to the formation of a number of metabolites, of which phenolic derivatives were prominent. In addition, S9-derived microsomes were able to catalyse the conversion of 3-nitroperylene to species which were able to bind to protein and DNA. Under the conditions employed in these binding studies, 3-nitroperylene appears to be acting like a simple PAH, and such experiments with very high concentrations of liver protein may be unrepresentative of the processes responsible for the mutagenesis of the compound. / Thesis / Master of Science (MSc)

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