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Re: FWD: A technique to measure DNA damage
Dear Radsafers,
The technique seems to be valuable for detecting base damage, base loss
and alkylations (very interesting for mutagenesis studies). It is not
for single strand breaks or double strand breaks. Therefore, the
technique is probably not of much interest for for studies of radiation
survival (models for cell survival of potential for the development of
predictive assays for normal and tumor tissue radiosensitivity).
Sincerely Yours,
Bjorn_Cedervall@hotmail.com , PhD
Karolinska Institutet
Stockholm, Sweden
------------------------------------------------------------
>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
>
>
>
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