|
|
|
|
|
|
|
(Prof. P.B. Farmer
with Drs. D.J.L. Jones, R. Singh, K. Brown, K. McLuckie)
|
|
|
|
 - This
section of the CBPG occupies a unique position within the UK academic
environment by virtue of its expertise in xenobiotic interactions with
cellular target sites as well as in the analysis of drugs and
their metabolites in biological fluids. State of the art techniques
available within the group include GC- and LC-MS-MS, HPLC with UV,
fluorescent and electrochemical detection, 32P-postlabelling
for determination of DNA damage, and immunoassay procedures for
detection of DNA adducts.The
group also has facilities for preparation of samples for, and access
to, accelerator mass spectrometry (AMS), which is currently the most
sensitive technique for the detection of isotopically labelled
xenobiotics in biological systems.
|
 - CBPG laboratory in the Biocentre
|
|
- One current emphasis of the group’s research is the involvement of
radical-induced damage to DNA in biological effects of exogenously
supplied chemicals. This approach is relevant to the identification of biomarkers of efficacy
or potential toxicity of putative chemopreventive agents. The group also has extensive experience in identifying
metabolite profiles for a wide range of compounds and techniques are
being developed to study polymorphisms in drug activating and
detoxifying enzymes.
|
|
|
|
 - The
compounds of main interest to the Group are mutagenic or
carcinogenic, and methodology has been developed to detect the
interactions of genotoxic molecules with DNA and proteins as a
marker of exposure to these compounds. Sensitivity of
detection of DNA adducts is below one adduct per 108 nucleotides.
The carcinogens of greatest interest at present are those from
environmental or food sources, although occupational and medicinal
exposures are also studied. Detailed studies have been carried
out, often involving extensive collaboration with EU scientists, on
populations exposed to a variety of environmental and occupational
genotoxins, including polycyclic aromatic hydrocarbons, low
molecular weight olefins, styrene, benzene, and acrylonitrile.
-
- Another
current emphasis of the group’s research is the involvement of
radical-induced damage to DNA in the biological effects of
exogenously supplied chemicals. This approach is relevant to the identification of biomarkers
of efficacy or potential toxicity of putative chemopreventive agents.
New approaches for determining oxidative DNA damage have been
developed, and these are being applied to populations exposed both
to environmental pollutants and to chemopreventive agents.
|
|
|
|
|
 - The
relationship between adducts and biological significance is in most
cases not completely understood. To investigate this we are
preparing carcinogen-modified oligonucleotides to study the
mutagenic consequences of adduct formation. Mutational events
and repair of DNA lesions are being investigated in cells
transfected with shuttle vector plasmids exposed to carcinogens, or
with plasmids containing site-specific carcinogen adducts, in order
to better understand the biological consequences of carcinogen
induced DNA damage.
|
|
