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Title: Unscheduled DNA synthesis as an indicator of genotoxicity
Author: Burlinson, B.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1995
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The escalating production of new chemical entities and the rising cost of long term toxicity studies has necessitated the development of a number of short-term terms. This thesis details the development and initial validation of assays in which the end point investigated was the measurement of DNA excision repair i.e. unscheduled DNA synthesis (UDS). Initially the assay was developed in primary rat hepatocytes and later progressed so that the exposure to the test material took place in vivo with subsequent radiolabelling of the repair sites taking place in vitro. In both cases the amount of repair taking place was measured by autoradiography. Due to the insensivity of the liver UDS assay to some classes of genotoxin and a requirement to measure effects in tissues other than the liver a second assay was designed which again used UDS as the end point but for which the test organ was the stomach, specifically the glandular mucosa. Using the special architecture of the mucosa a system was developed where UDS could be measured (after in vivo exposure to the test agent and radiolabel) by scintillation counting. A number of test agents were investigated including known carcinogens, gastric irritants and those activated in the stomach by nitrosation. Results of both assays are given and their relevance to genotoxicity testing discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available