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Title: Development of class-specific and compound specific antibodies for the detection, identification and exposure monitoring of genotoxic carcinogens
Author: Ball, Lathan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Mercapturic acids are urinary metabolites which signal exposure to genotoxic compounds. Carefully designed hapten-protein conjugates and a judicious screening strategy has enabled the generation of compound and class-specific antibodies which bind mercapturic acids. S-phenylmercapuric acid (S-PMA) is a highly specific and sensitive marker of benzene exposure. A monoclonal antibody reactive with S-PMA has been generated. The immobilised antibody retains immunoreactivity and can be used to enrich S-PMA from the urine of benzene exposed workers. The performance of the immunoaffinity column has been validated by comparison with data obtained from GC/MS analysis of urine from benzene exposed workers (range 12-168ug/1. corr. coeff. 0.98, n=23). Furthermore immunoaffinity chromatography facilitates the quantitative determination of urinary S-PMA by HPLC. Bioconcentration of S-PMA from the urine of benzene exposed workers has permitted the quantification of S-PMA by HPLC at 8 hour Time Weighted Average exposures of around 1ppm. Monoclonal antibodies to low molecular weight mercapturic acids (eg. S-(2-hydroxyethyl)mercapturic acid) were generally of too low affinity for practical application. As an alternative approach antibodies to adducted protein were investigated. Antibody 4D3 binds the adducted N-terminal heptapeptide released from the alpha-chain of haemoglobin by trypsin hydrolysis. Initial studies suggest antibody 4D3 can bind the adducted heptapeptide in whole haemoglobin. This may facilitate the determination of adducted haemoglobin in biomonitoring studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available