Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.470714
Title: Investigations into the effects of alkylation of deoxyribonucleic acid in baby hamster kidney cells by N-methyl-N'-nitro-N-nitrosoguanidine
Author: Robinson, A. C.
Awarding Body: Aberdeen University
Current Institution: University of Aberdeen
Date of Award: 1978
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Abstract:
The cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) towards asynchronous populations of baby hamster kidney (BHK) cells was correlated with the effects of alkylation-induced damage to parental and nascent DNA. The formation and repair of single-strand breaks in DNA following MNNG treatment was studied. Breakdown of parental DNA was found to be dose-dependent and repair of this damage was only evident following doses of MNNG leading to greater than 75% survival. Approximate extents of DNA methylation were calculated and found to be in reasonable agreement with published values for other cell lines at equivalent toxicities. MNNG treatment resulted in an immediate dose-dependent depression in the rate of DNA synthesis. A dose of 5 μg/ml MNNG resulted in a substantial reduction in thymidine uptake into acid-soluble pool(s); no such reduction was observed at doses of less than 1 μg/ml. Nascent DNA of MNNG-treated cells was of lower molecular-weight than that synthesised in control cells and its ligation to high molecular weight was shown not to be inhibited by subsequent treatment with 1mM caffeine. 1mM caffeine was found to potentiate the lethal effect of MNNG, to reduce the MNNG-induced depression in the rate of DNA synthesis in non-alkylated cells (an effect shown not to be related to thymidine uptake into acid-soluble pool(s)). DNA synthesised in the presence of caffeine was smaller than that synthesised in its absence in both alkylated and control cells. It is proposed that these effects of caffeine are due to its inducing an increase in the number of replicon initiation sites. It is proposed that BHK cells possess a caffeine-insensitive post-replication repair mechanism following MNNG treatment, which differs from that operating following ultraviolet irradiation which had previously been shown to be caffeine sensitive.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.470714  DOI: Not available
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