Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous carcinogenic compounds that are produced by burning of carbon-based compounds like organic matter, oil, and coal. They are found in burnt food, soot, and in cigarette and other smokes. PAHs’ carcinogenicity comes from their ability to cause mutations by binding to DNA, which makes them tumor initiators and also allows them to assist in tumor progression. This technology is two monoclonal antibodies that recognize the DNA- and protein-adducts of benzo[a]pyrene diol epoxide (BPDE), an oxidized form of the PAH benzo[a]pyrene. They have been developed into an assay that can quantify the amount of BPDE in white blood cells and can be used to screen patients for exposure to BPDE.
Assays based on monoclonal antibodies 5D11 and 8E11 detect, respectively, BDPE-DNA and BDPE-protein adducts with high specificity and sensitivity
This technology consists of the monoclonal antibodies 5D11, which detects BDPE-DNA adducts, and 8E11, which detects BDPE-protein adducts. The antibodies are produced in vitro, and can thus be developed in limitless supply in the laboratory. Furthermore, BDPEs can be produced in different geometric arrangements, and both antibodies can detect adducts of multiple geometries while maintaining a high specificity for the BDPE-DNA or -protein adduct.
This technology has been used in multiple screening experiments and to monitor environmental exposure to PAHs, including the screening of breast cancer tissues for the presence of PAHs.
Lead Inventor:
I. Bernard Weinstein, Ph.D.
Applications:
- Screening test for benzo[a]pyrene exposure
- Monitoring levels of BDPE-DNA or BDPE-protein levels in at risk populations
- Diagnostic test for identifying cause of tumor damage and progression
- Research tool for studying the mechanism of action of PAH carcinogenicity
Advantages:
- Antibodies can be produced in limitless supply in vitro
- Higher specificity for BDPE in human samples than other PAH screening tests
Patent Information:
Copyright
Tech Ventures Reference: IR 31
Related Publications:
Santella RM, Lin CD, Cleveland WL, Weinstein IB. “Monoclonal antibodies to DNA modified by a benzo[a]pyrene diol epoxide.” Carcinogenesis. 1984 Mar;5(3):373-7.
Santella RM, Lin CD, Dharmaraja N. “Monoclonal antibodies to a benzo[a]pyrene diolepoxide modified protein.” Carcinogenesis. 1986 Mar;7(3):441-4.
Santella RM. “Monitoring human exposure to carcinogens by DNA adduct measurement.” Cell Biol Toxicol. 1988 Dec;4(4):511-6.
Hsu TM, Liu TM, Amin S, Geacintov NE, Santella RM. “Determination of stereospecificity of benzo[a]pyrene diolepoxide-DNA antisera with site-specifically modified oligonucleotides.” Carcinogenesis. 1995 Sep;16(9):2263-5.
Santella RM, Gammon MD, Zhang YJ, Motykiewicz G, Young TL, Hayes SC, Terry MB, Schoenberg JB, Brinton LA, Bose S, Teitelbaum SL, Hibshoosh H. “Immunohistochemical analysis of polycyclic aromatic hydrocarbon-DNA adducts in breast tumor tissue.” Cancer Lett. 2000 Jun 30;154(2):143-9.
Motykiewicz G, Małusecka E, Michalska J, Kalinowska E, Włoch J, Butkiewicz D, Mazurek A, Lange D, Perera FP, Santella RM. “Immunoperoxidase detection of polycyclic aromatic hydrocarbon-DNA adducts in breast tissue sections.” Cancer Detect Prev. 2001;25(4):328-35.
