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Title: Molecular analysis of genotoxin induced mutations in rodents
Author: Song, H.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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The Restriction Site Mutation (RSM) assay was employed to study p53 gene mutations induced in vivo by N-ethyl-N-nitrosourea (ENU), cyclophosphamide (CP), and in vitro by 4-Nitroquinoline 1-oxide (4NQO). The effectiveness of the RSM assay was further confirmed by detecting 193 mutant sites in liver, kidney, lung, and testis of animals treated in vivo, as well as in mammalian cell culture treated in vitro. Rare spontaneous germline mutations were for the first time detected by the RSM assay. This further emphasizes the sensitivity of the RSM assay. These results imply that the RSM can be used in germline mutagenesis study providing data not currently available. Relatively, more mutations were detected in intron regions than in exon regions of the p53 gene. Mutation strand specificities, neighbouring base influences and mutation persistence were demonstrated and analysed in this study. A new method to quantify RSM products was developed in this study, which applied an external dilution series of genomic DNA. Mutation frequency was calculated at each of the restriction sites studied. This can be used to compare mutability between different gene regions and in different species. The RSM assay was also employed to compare the mutability of an endogenous p53 gene and inserted transgenic LacZ gene in transgenic MutaTMmouse. The results obtained implied that the p53 gene was perhaps more susceptible to the mutagen ENU than that of LacZ gene in MutaTMmouse testes. If so, the integrated LacZ gene might not be necessarily representative of endogenous mutation targets of environmental carcinogens.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available