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Title: Sister chromatid exchange and chromosome aberrations in human lymphocytes vs point-mutational damage in bacteria : a study comparing different methods for investigating DNA damage by chemicals
Author: Herbert, Anthony
ISNI:       0000 0001 3553 9653
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1982
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SCE in human lymphocytes has been investigated as an indicator of chemical mutagenesis. The sensitivity, accuracy and feasibility of application of SCE as an in vitro screening test has been evaluated against cytogenetic aberrations and the Ames test. Throughout, attention has been paid to technical detail. The FPC method has been modified and improved allowing sister chromatid differential staining in a fraction of the time of published methods. Before observing SCE's in chemically treated lymphocytes the spontaneous SCE frequency in human lymphocytes was investigated for natural variation eg due to donor age or sex differences. A method is presented for improved yields of mitotic lymphocytes at 72 hours. In the Ames test excision repair defective bacteria and plasmid bearing strains have been used in combination with repair competent strains to observe the modifying effect of DNA repair systems on DNA mutation. A method is proposed to allow quantitative estimates to be made of mutation frequency. The induction of SCE and cytogenetic aberrations in human lymphocytes and point-mutation in Salmonella has been investigated following exposure to a range of selected direct-acting chemical mutagens. The compounds include:- the alkylating agent, ethyl methane sulphonate; the pairs, methyl nitroso urea/ethyl nitroso urea and mitomycin C/ decarbamoyl NMC; a pyrrole alcohol and 2 monofunctional derivatives; the DNA intercalating agent, hycanthone methane sulphonate. There is a quantitative relationship between SCE and point-mutational damage of a base-substitutional nature although the relationship is different for each chemical investigated. The relationship between DNA crosslinks and SCE remains unclear. The relationship between SCE and specific DNA alkylation products, particularly at the 0-6 and N-7 positions of guanine is discussed. DNA intercalation leads to chromosome breakage rather than SCE. The concept of mutagenesis/carcinogenesis has been reviewed. The mechanism by which SCE's are formed and their biological significance is considered.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry