Immunologic Methods for the Detection of Carcinogen Adducts in Humans
Immunologic methods are now available for the sensitive detection and quantitation of carcinogen-DNA adducts. Monoclonal and polyclonal antibodies have been developed against a number of specific adducts as well as against UV-damaged DNA (Poirier, 1981; Santella, 1988). Antibodies can be developed against either the carcinogen adduct covalently coupled to carrier protein or the modified DNA electrostatically complexed to methylated bovine serum albumin. These antibodies can be used in highly sensitive competitive enzyme-linked immunosorbent assays (ELISA) with color- or fluorescence endpoint detection. Since femtomole (10-15) sensitivities are readily attainable, DNA adduct levels in the range of 1/108 nucleotides can be measured. With monoadduct-specific antibodies, higher sensitivities may be obtainable if large amounts of DNA are available and the adduct is isolated by various chromatographic procedures before quantitation in the ELISA. Table 1 lists the monoclonal antibodies recognizing carcinogen-DNA adducts which we have developed to date. Several of these antibodies, including those recognizing aflatoxin, benzo(a)pyrene diol epoxide and 8-methoxypsoralen-DNA adducts, have been applied to adduct detection in humans.
KeywordsPsoriasis Patient Competitive ELISA Adduct Level Skin Irradiation Aryl Hydrocarbon Hydroxylase Activity
Unable to display preview. Download preview PDF.
- Busby, W. F., and Wogan, G. N., 1984, Aflatoxins. in: “Chemical Carcinogens”. Searle, C. D., ed., ACS, Washington, DC.Google Scholar
- Harris, C. C., Vahakangas, K., Newman, J. M., Trivers, G. E., Shamsuddin, A., Sinopoli, N., Mann, D. L., and Wright, W. E. 1985, Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers. Proc. Natl. Acad. Sci. USA, 82: 6672.PubMedCrossRefGoogle Scholar
- Perera. F. P., Mayer, Jl, Jaretzki, A., Hearne, S., Brenner, D., Young, T. L., Fishman, H. K., Fishman, H. K., Grimes, M., Grantham, S., Tang, M. X., Tsai, W. Y., Santella, R. M., 1989, Comparison of DNA adducts and sister chromatid exchange in lung cancer cases and controls. Cancer Research, 49: 4446.PubMedGoogle Scholar
- Santella, R. M., Gasparo, F. P., and Hsieh, L. L., 1987, Quantitation of carcinogen-DNA adducts with monoclonal antibodies. Prog. Exper. Tumor Res., 31: 63.Google Scholar
- Santella, R. M., Yang, X. Y., DeLeo, V. A., and Gasparro, F. P., 1988, Detection and quantification of 8-methoxypsoralen-DNA adducts, in: Bartsch, H., Hemminki, K., and O’Neil, I.K. ed., “Methods for Detecting DNA Damaging Agents in Human: Applications in Cancer Epidemiology and Prevention”. IARC, Lyon.Google Scholar
- Weston, A., Trivers, G., Vahakangas, K., Newman, M., and Rowe, M., 1987, Detection of carcinogen-DNA adducts in human cells and Antibodies to These Adducts in Human Sera. Prog. Exper. Tumor Res., 31: 76.Google Scholar
- Wogan, G. N., 1976, Aflatoxins and their relationship to hepatocellular carcinoma, in: “Hepatocellular Carcinoma,” Okuda, K. and Peters, R.L., ed., John Wiley and Sons, New York.Google Scholar
- Yang, X. Y., and Santella, R. M., 1987, Development of monoclonal antibodies to acetylaminofluorene modified DNA and poly(dG-dC)-poly(dG-dC)., in: Carcinogenic and Mutagenic Responses to Aromatic Amines and Nitroarenes., King. C. M., Romano, L. J., and Schuetzle, D., ed., Elsevier, New York.Google Scholar
- Yang, T. L., and Santella, R. M., 1988, Development of techniques to monitor for exposure to vinyl chloride: monoclonal antibodies to ethenoadenosine and ethenocytine. Carcinogenesis, 9: 5892.Google Scholar