Detecting Hazardous Agents

About

Summary Increasing numbers of environmental agents are being found to be harmful and, of these, many arecarcinogens which promote the formation of covalently linked DNA-proteincomplexes (DPCs). DPCs induce tumor formation by disrupting DNA replication anddeactivating tumor suppressor genes. Therefore, it is important to be able todetect and evaluate the carcinogenic potential of harmful chemicals which causeDPC formation in order to avoid exposure to them. This can be done by measuringthe ability of suspected carcinogens (including ultraviolet and gammaradiation) to promote the attachment of proteins to DNA. Many attempts havebeen made to develop rapid, sensitive methods for detecting DNA-proteincrosslinks which occur in cells exposed to crosslinking reagents. The mostwidely used methods are hampered by cumbersome, time-consuming assays involvingindirect measurement of DPC formation, which can not handle large numbers ofsamples.   Description of the Project: Dr. Costa has devised a new highly sensitive,reproducible, rapid, and accurate method for detecting DNA-protein complexes incells following their exposure in vivo or in culture. He hasdemonstrated 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 culturedcells. The method also successfully detects DPCs in white blood cells takenfrom animals exposed to chromate. A study examining the peripheral white bloodcells of welders exposed to nickel and chromium-containing welding fumes showedthey had elevated DPCs compared to unexposed control workers, indicating anelevated biomarker related to nickel and chromium exposure. DPCs may serve as abiomarker of exposure to crosslinking agents and as an early indicator of theconsequences of exposure, such as cancer.   Applications: NYU is seeking a partner to develop this novel assay as a detection kit foruniversal testing of suspected carcinogens. The assay provides ascreening method to: Evaluate the carcinogenic potential of organic andmetal chemical agents used in manufacturing and processing steps in industry Monitor and measure the exposure of workers to hazardous chemicals in thework environment Test predisposition of individuals to exhibitinggenetic damage such as deletions.