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Title: The human lymphoblastoma cell line AHH-1
Author: Guest, R. D.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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The human lymphoblastoid cell line AHH-1 (which expresses CYP1A1) and the metabolically competent derivative MCL-5 (which expresses CYP1A2, 2A6, 2E1, 3A4 and epoxide hydrolase), have been shown to be capable of detecting a variety of pro-genotoxins in the in vitro binucleate micronucleus assay. In these studies, it was possible to identify the inducibility of micronuclei by: tobacco particular matter (TPM); diesel particulate matter (DPM); "Sea Empress" slick oil; and crude oil using the binucleate micronucleus assay. A positive increase in micronuclei in mammalian binucleate cells was registered for MCL-5 cells exposed to both Slick (0.5 mg/ml) and Crude oil (0.063 mg/ml) and a positive increase in micronucleated binucleate cells was also presented in both cell lines when exposed to either DPM or TMP. These micronuclei were induced by both aneugenic and clastogenic mechanisms. Increased in mutations occurred in the tk mutation assay in AHH-1 for DPM (5μm/ml) and TPM (10μg/ml); in the hprt mutation assay AHH-1 mutations increased significantly for DPM (10μg/ml) and TPM (5μm/ml); and a significant increases in mutations was identified in MCL-5 for both assays and compounds at 5μg/ml. As the identification of micronuclei (clastogenic or aneugenic) and the production of mutations, by TPM and DPM, were shown it was appropriate to investigate whether they were due to large adducts using the 32P-postlabelling assay and/or due to small oxidative adducts by Fapy-DNA-glycosylase. Using both restriction enzyme and sequencing analysis it was possible to identify a mutation within the p53 gene of both cell lines. However, after annexin V labelling distinguished that DNA damage induced cell death was occurring the problem of using the cell lines as a model was totally vindicated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available