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Title: Investigations into free radical production by asbestos and man-made vitreous fibres
Author: Pickering, Pamela
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1994
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Occupational exposure to asbestos is associated with increased incidence of lung fibrosis, lung cancer and mesothelioma. Concern has been expressed that other mineral fibres could have similar effects. Uncertainties arise through inadequate understanding of the mechanisms underlying disease. This study examined the role of oxygen free radicals in the toxicity of asbestos and man-made vitreous fibres (MMVF). Several mineral fibres, as a consequence of their iron contents, are able to generate hydroxyl radicals in aqueous solution. Here, crocidolite asbestos and size selected MMVF (the Thermal Insulation Manufacturers' Association fibres), of known iron contents, were compared in their ability to hydroxylate guanine, either as 2-deoxyguanosine or in isolated calf thymus DNA in aqueous solutions using 8-hydroxydeoxyguanosine (8-OHdG) as an end point. The relative activities of the fibres varied depending on experimental conditions and sample characteristics. Activity could not be correlated with iron content. RCFl and MMVF21 were particularly active under mildly acidic conditions. No fibre tested, (including crocidolite asbestos and the carcinogenic zeolite, erionite), induced 8-OHdG formation in cellular DNA, indicating that oxidative DNA damage may not be involved in fibre induced neoplasia. Free radicals contributed to the cytotoxicity of crocidolite but this was slight in comparison to the physical effects of fibre dimension. The MMVF generally demonstrated similar low toxicities. The high catalytic activity of MMVF21 and RCFl was not reflected in measures of cytotoxicity (arachidonic acid and lactate dehydrogenase release and colony forming efficiency) although MMVF21 induced significantly increased transformation frequency in C3H10T1/2 cells. By comparing the catalytic activities of the MMVFs with their in vitro and in vivo toxicity it was concluded that free radicals are not significant mediators of fibre pathogenesis. The measurement of free radical activity in cell free systems was considered to be of little value in the hazard assessment of fibres.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available