|
Principal Investigator:
Max
Costa, Ph.D., Department of Environmental Medicine and
Pharmacology
New York University School of Medicine
Increasing numbers of
environmental agents are being found to be harmful and, of these, many are
carcinogens which promote the formation of covalently linked DNA-protein
complexes (DPCs). DPCs induce tumor formation by disrupting DNA replication
and deactivating tumor suppressor genes. Therefore, it is important to be
able to detect and evaluate the carcinogenic potential of harmful chemicals
which cause DPC formation in order to avoid exposure to them. This can be
done by measuring the ability of suspected carcinogens (including ultraviolet
and gamma radiation) to promote the attachment of proteins to DNA. Many attempts
have been made to develop rapid, sensitive methods for detecting DNA-protein
crosslinks which occur in cells exposed to crosslinking reagents. The most
widely used methods are hampered by cumbersome, time-consuming assays involving
indirect measurement of DPC formation, which can not handle large numbers
of samples.
Description of the
Project:
Dr. Costa has devised a new highly sensitive, reproducible,
rapid, and accurate method for detecting DNA-protein complexes
in cells following their exposure in vivo or in
culture. He has demonstrated that his new method (which does not
require the use of radioactivity) detects DPCs induced by chromate,
cis-Pt(II), diammine dichloride, formaldehyde, and alkylating
agents, in a dose-dependent manner in cultured cells. The method
also successfully detects DPCs in white blood cells taken from
animals exposed to chromate. A study examining the peripheral
white blood cells of welders exposed to nickel and chromium-containing
welding fumes showed they had elevated DPCs compared to unexposed
control workers, indicating an elevated biomarker related to nickel
and chromium exposure. DPCs may serve as a biomarker of exposure
to crosslinking agents and as an early indicator of the consequences
of exposure, such as cancer.
Applications:
NYU is seeking a partner to develop this novel assay as a detection
kit for universal testing of suspected carcinogens.
The assay provides a
screening method to (i) evaluate the carcinogenic potential of organic and
metal chemical agents used in manufacturing and processing steps in industry,
(ii) monitor and measure the exposure of workers to hazardous chemicals in
the work environment and (iii) test predisposition of individuals to exhibiting
genetic damage such as deletions.
Patent Status:
A patent application covering this novel technology for detecting
and screening carcinogens has been filed in the United States.
For further information please contact:
New York University
Industrial Liaison/Technology Transfer
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189
|
