| Summary: | Rapid development of the chemical industry over the past two decades makes
the study of the effects of chemical substances (such as benzene) on the
human body essential, Benzene toxicity involves both bone marrow
depression and Ieukemogenesis caused by damage to various classes of
hematopoietic cells and a variety of hematopoietic cell functions. Studies of
the relationship between the metabolism and toxicity of benzene indicate that
several metabolites of benzene play significant roles in generating benzene
toxicity. Benzene is metabolized, primarily in the liver, to a variety of
hydroxylated and ringopened products that are transported to the bone
marrow where subsequent secondary metabolisms occur.
Maintenance of the genomic integrity is of crucial importance for all
organisms. Damage to the DNA that makes up human genes is constantly
inflicted by a large number of agents and can have severe effects if it persists.
Modification of DNA can lead to mutations, which alter the coding sequence of
DNA and can lead to cancer in mammals. Other DNA lesions interfere with
normal cellular transactions such as DNA replication or transcription, and are
deleterious to the cell. Thus it is obvious that the stability of the genome must
be under continuous surveillance. This is accomplished by DNA repair
mechanisms, which remove DNA lesions in an error-free, or in some cases,
error-prone way. Defects in DNA repair give rise to hypersensitivity to DNA
damaging agents, accumulation of mutations in the genome, and finally to the
development of cancer and various metabolic disorders.
The alkaline single cell gel electrophoresis assay (comet assay) was applied
to study the occurrence of DNA damage and repair in peripheral lymphocytes
of 27 experimental human subjects with occupational exposure to benzene
and 9 control human subjects with no occupational exposure to benzene.
Two blood samples (pre-shift and after-shift respectively) were obtained from
each of the control as well as the experimental subjects. After
electrophoresis, scoring was done by using the CASP software program. Two
of several variables were of primary interest, i.e., Tail DNA% and Tail Moment. Statistical analysis clearly indicated that significant differences exist
between pre-shift and after-shift data for both variables. Results revealed that
there are also different behaviour patterns for the experimental and control
groups, pre-shift and after-shift, for both variables during all stages of the
comet assay. It became evident for both Tail DNA%-data and Tail Momentdata
that DNA damage was indeed present at the exposed (experimental)
group of workers. For the experimental group, after-shift data exceeded pre-shift
data in general. Different behaviour was noticed between the
experimental and control-data during the repair process. Also, the initial pre-shift
data-values of the experimental group, is much higher (about 9%) than
that of the control group, which may be an indication of a carried-over effect
which may exist from the previous shift, due to the exposure to benzene.
After-shift urine samples were also obtained from the experimental and
control subjects and analysed for urinary trans-trans-muconic acid (ttMA), a
metabolite of benzene, with the aid of a high-performance liquid
chromatography (HPLCIUV) detector. The exposed workers showed a
markedly higher (1,8 times) ttMA mean value than the control persons, and
the two-sample t-test confirmed this significant difference. === Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2004.
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