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Title: An investigation of bioactivation of promutagens by genetically engineered human cell lines
Author: Doherty, A. T.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1996
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The human lymphoblastoid cell line AHH-1 and the metabolically competent derivative MCL-5 (CYP1A2, 2A6,3A4, 2E1 and epoxide hydrolase), have demonstrated their ability to detect a variety of pro-genotoxins in the in vitro micronucleus assay including benzo(a)pyrene, 2-acetylaminofluorene, aflatoxin B1 and sterigmatocystin. This study demonstrated the induction of kinetochore positive micronuclei in MCL-5 cultures exposed to trichloroethylene which are thought to be due to its metabolism in MCL-5 cells to chloral hydrate which gives the same induction of kinetochore positive micronuclei. A group of chlorinated hydrocarbons with potential environmental and occupational exposure have been investigated in the cell lines. Carbon Tetrachloride, Methylene Chloride, 1,1,3-Trichloropropene, 2,3-Dichlorobutane, and 1,1,2-Trichloroethane, induced micronuclei in the metabolically competent MCL-5 and H2E1 cells, 2,3-Dichlorobutane and 1,1,2-Trichloroethane induced kinetochore positive micronuclei demonstrating that the combination of metabolically competent human cell lines with the micronucleus assay and kinetochore labelling can detect the metabolism of xenobiotics to aneugenic species. The therapeutic drugs omeprazole and tamoxifen have induced kinetochore negative micronuclei in the MCL-5 cells that were not present in AHH-1 cells. This may be due to the production of genotoxic metabolics of these drugs in MCL-5 cells. The cytogenetic analyses by G-banding and FISH techniques have allowed the detection and identification of translocations within the cell lines and the stability of these translocations throughout the periods of cell culture.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available