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FWD: A technique to measure DNA damage
The following message was posted on 29 May 1998 on the RISKANAL mailing list by
Dr. Steven Hrudey of the University of Alberta. It may also be of interest to
some RADSAFE readers.
Best regards.
Jim Dukelow
Pacific Northwest National Laboratory
Richland, WA
jim.dukelow@pnl.gov
===============
From: Steve Hrudey [Steve.Hrudey@UAlberta.Ca]
Sent: Friday, May 29, 1998 3:36 PM
Subject: Re: RISKANAL digest 1059
Major Breakthrough in Assessing DNA Damage and Repair
Department of Public Health Sciences, University of Alberta, Edmonton,
Canada.
Faculty of Medicine and Oral Health Sciences researchers at the
University of Alberta, Dr. X. Chris Le, Dr. Michael Weinfeld and their
colleagues, published in the May 15 edition of Science (280: 1066 -
1069; editorial commentary on 1101-1102) a report on a new
ultrasensitive technique for measuring DNA damage.
This technique has resulted in a 10,000 to 100,000 fold increase in
sensitivity over the current state-of-the-art for detecting DNA damage.
The sensitivity of this advance allows, for the first time, the accurate
detection of DNA damage at realistic low levels which are relevant to
environmental exposures to DNA damaging agents like those which initiate
cancer (e.g. ionizing radiation, chemical carcinogens).
This new technique couples immunochemical recognition (the process by
which the body recognizes foreign substances) with capillary
electrophoresis (an advanced separation technique) and laser-induced
fluorescence (a highly sensitive detection technique) (patent pending)
The new technique is also extremely specific which makes it very
powerful for studying the mechanisms of DNA damage and repair. These
capabilities stand to greatly facilitate advances in many aspects of
research on cancer treatment and it should open valuable new avenues of
investigation in a wide range of health research from studies on aging
processes to evaluation of cancer causation and therapy. Because the
method is based on antibody detection (the immune response to foreign
substances) it can be adapted to a wide range of other very specific
forms of DNA damage and some of these new applications are currently
under development.
The prospects for advances in risk assessment resulting from this
discovery are exciting.
Until now, risk assessment has emphasized only carcinogen exposure, with
the assumption that cancer risk was determined primarily by the degree
of exposure to DNA-damaging carcinogens, even at very low levels. A new
perspective is that cancer risk for many low level environmental
exposures may be determined more by a person's DNA repair capability
than by that person's low level exposure to carcinogens. This discovery
will allow validation of that new perspective by allowing the direct
study of DNA repair. This capability can dramatically improve our
approaches to quantitative cancer risk assessment and ultimately our
ability to set sound priorities for environmental health.
The discovery by Dr. Le and his colleagues offers the prospects of being
able to measure DNA damage with sufficient sensitivity and specificity
to allow testing of dose-response models for low level cancer risk from
individual carcinogens. The paper in Science describes an experiment to
measure DNA repair caused by ionizing radiation. This showed that
giving a low dose of radiation to human tumour cells, 4 hours before a
clinical dose of radiation (the level used in cancer treatment) resulted
in more rapid DNA repair than without the prior low dose, likely by
stimulating the DNA repair enzymes. This finding is the first direct
evidence, concerning DNA repair, of a controversial theory that a low
level of radiation may not be strictly harmful but may in fact be
helpful by stimulating more rapid repair of DNA damage. There are also
substantial prospects of being able to automate the procedures to allow
for monitoring of humans who may are exposed to carcinogens in the
workplace or from environmental contamination sources for evidence of
carcinogen-specific DNA damage.
In their editorial summary, Dr. Richard Peters and Robert Sikorski
commented: "Armed with such a specific and sensitive assay, one can only
imagine some of the possibilities. For instance, scientists should more
easily detect the type and frequency of DNA lesions in living tissues
after exposure to environmental radiation or chemical carcinogens.
Monoclonal antibodies targeted at other base lesions could be used to
look at a series of DNA or RNA lesions. The system could also be used to
monitor protein adducts or drug metabolites, as long as monoclonal
antibodies are raised to specific moieties. There is little doubt that,
over the forseeable future, we will see an explosion in the number of
reports making use of this seminal technique in the various fields of
life sciences, from toxicology to molecular biology."
This work was done in a collaborative manner between Dr. X. Chris Le and
Dr. Michael Weinfeld with key input from Dr. S.A. Leadon, University of
North Carolina School of Medicine. The other co-authors are Dr. James
Xing, a post-doctoral fellow working with Dr. Le and Ms. Jane Lee,
working with Dr. Weinfeld. This discovery arose from "curiosity driven"
research funded through an individual research grant to Dr. Le from the
Natural Sciences and Engineering Research Council of Canada, from the
National Cancer Institute of Canada and the Alberta Cancer Board to Dr.
Weinfeld and from U.S. National Institutes of Health to Dr. Leadon. Dr.
Le was recruited through a grant to Dr. Hrudey's Eco-Research Chair in
Environmental Risk Management from the Alberta Heritage Foundation for
Medical Research.
For information, contact:
Dr. Chris Le,
Assistant Professor of Environmental Health Sciences
at (403) 492-6416;
fax (403) 492-0364
e-mail: xc.le@ualberta.ca;
www.ualberta.ca/~envrisk/erm.html
Dr. Michael Weinfeld,
Associate Professor of Experimental Oncology
at 011-44-171-269-3926;
fax 011-44-171-269-3801
e-mail: weinfeld@icrf.icnet.uk
Steve E. Hrudey, Ph.D., P.Eng.
Professor of Environmental Health Sciences
Eco-Research Chair in Environmental Risk Management
13-103 Clinical Sciences Building
University of Alberta, Edmonton CANADA T6G 2G3
Phone: 403-492-6807 Fax: 403-492-0364
E-mail: Steve.Hrudey@UAlberta.Ca
Web Page: http://www.ualberta.ca/~envrisk/erm.html