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Validation of biomarkers for improved assessment of exposure and early effect from exposure to crystalline silica

MSc (Med) Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / This is the third phase of a project to identify, confirm, and operationalise biomarkers for
crystalline silica dust exposure that could be used for surveillance of dust exposure levels
in South African mines. The first phase of the project involved a comprehensive review
of the relevant literature [Gulumian et al., 2006] from which ten potential biomarkers of
effect were identified as being worthy of further investigation. The second phase of the
project examined the ten identified biomarkers in silica dust-exposed and unexposed
black male subjects [Murray et al., 2006]. Two of the ten short listed biomarkers, namely
erythrocyte glutathione peroxidase (GPx) and serum Clara cell protein 16 (CC16), were
found to have significantly reduced levels in the silica dust-exposed versus unexposed
subjects. In addition, the biomarkers were found to be unaffected by HIV sero-status,
smoking, age and the presence of silicosis. As a result, this third phase of the project
aimed to confirm the levels of and further analyze GPx and CC16 in miners exposed to
crystalline silica dust.
This third phase involved the measurement of the levels of erythrocyte GPx and serum
CC16 in 80 adult male gold miners upon their return from leave and then again two to six
months after they had returned to work (involving exposure to crystalline silica). Before
the field work was conducted, however, the optimal operational parameters for the
biomarkers (namely storage temperature, delay in time between blood collection and
separation, laboratory temperature and storage duration) were established. The results of
these optimization experiments were used to develop Standard Operating Procedures
(SOPs) for biomarker specimen handling and storage under field conditions, and for
laboratory assays.
In this phase, the findings of the second phase were confirmed in that the levels of GPx
and CC16 were lowered in miners exposed to crystalline silica dust and were unaffected
by age, race and cigarette smoking. In addition, while CC16 was unaffected by the
presence of radiological silicosis, GPx may have been affected. Finally, the decrease in
the levels of GPx activity and CC16 concentration observed in the study were unaffected
by the level of silica dust exposure (high or low) as determined by job category or by the
duration of crystalline silica exposure.
Regarding the levels of GPx activity, the results suggested that GPx levels decrease after
two to six months of chronic exposure to crystalline silica dust and remain decreased
(throughout the working week and over a weekend) and then increase or even recover to
normal levels during a period of leave. It was therefore concluded that GPx activity levels
rise and fall, in response to silica dust exposure, gradually and over periods of some time,
possibly months.
The CC16 results were, however, less promising. After two to six months of chronic
exposure to crystalline silica dust there was a significant change in CC16 on a
Wednesday afternoon following an 8-hour shift and during the duration of a shift. In
addition, there is the possibility that the observed changes were due to a time-dependent
diurnal variation in the CC16 levels.
It was concluded that the results of the current phase warrant further research into the use
of erythrocyte GPx and serum CC16 as biomarkers of early effect from crystalline silica
exposure.

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/7972
Date13 April 2010
CreatorsMakinson, Kerry Sue
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf, application/pdf

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