Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.477920
Title: Molecular interactions in the assessment of the genotoxicity of alkylating agents
Author: Wooder, Michael F.
ISNI:       0000 0001 3572 1615
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1977
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Abstract:
The recognition and subsequent demonstration, in vitro, of the alkylating potential of dichlorvos has led to a suspicion that this triester of phosphoric acid may be a mutagen and a carcinogen. Despite consistently negative results obtained in mammalian mutagenicity and carcinogenicity tests it was never-the-less important to investigate the alkylating reactivity in vivo. In the experiments described in this thesis, male CFE rats were exposed to atmospheres containing 0,064ug 1[-1] of [Me-[14]C] dichlorvos (113Ci.mol[-1]) for 12 hours. Analysis of the DNA from the total soft tissues from 20 rats revealed no methylation at the N-7 atom of guanine moieties. A comparative study with [methyl-[14]C]methanesulphonate gave rise to a readily detectable extent of methylation of the N-7 atom of the guanine moieties in DNA. The limit of detection of methylation of the DNA in the dichlorvos study was one methyl group per 5.7 x 10[11] nucleotide units. The proportion of the administered dose that would be consumed in this hypothetical reaction would be 0.000001%. The exposure period employed in this study (12h) constituted a significant fraction of the half-live of 7-methylguanine moieties in DNA (3 days) and the current findings therefore indicate that dichlorvos would not methylate the DNA of mammalian tissues even when it is inhaled continuously for protracted periods of The administration of radiolabelled adenine, guanine, methionine and formate to otherwise untreated rats, gave rise to the excretion of radiolabelled methylated purines in urine. This finding indicates that the detection of radio- labelled methylated purines, per se, in the urine of animals exposed to methyl-labelled methylating agents does not constitute evidence for the spontaneous methylation of the purine moieties of nucleosides and nucleic acids by methylating agents, in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.477920  DOI: Not available
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