Determination of Carcinogen Exposure by Immunological Techniques

  • Lars O. Dragsted


Humans are exposed to carcinogens from a variety of sources including food, drinking water, air, and the working environment. A few of these carcinogens have been identified epidemiologically, but the majority have been identified by animal bioassays and their impact on human cancer is not well established. The mathematical quantitation of human cancer risk from exposures to animal carcinogens relies on the validity of animal to man extrapolations. Several pieces of information could increase the validity of such extrapolations. Among these, comparative pharmacokinetic data from the relevant test animals and from man are particularly important because these data will tell to what extent the compound is handled similarly and whether it elicits toxicity by the same mechanism in the two species. The quantitation of human risk is also highly dependent on data providing the actual human exposure levels. Futhermore, large interindividual variations in exposures and in pharmacokinetics are most probably found for most carcinogens in human populations. Therefore this variability should also be validated in order not to underestimate the risk to certain groups or individuals.


Polycyclic Aromatic Hydrocarbon Adduct Level Carcinogen Exposure Large Interindividual Variation Sensitive Immunoassay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamkiewicz, J., Drosdziok, W., and Eberhardt, W., Langenberg, U., and Rajewsky, M. F., 1983, High-affinity monoclonal antibodies specific for DNA components structurally modified by alkylating agents, Banbury Report 13: 265.Google Scholar
  2. Adamkiewicz, J., Nehls, P., and Rajewsky, M. F., 1984, Immunological methods for detection of carcinogen-DNA adducts, In: “Monitoring human exposure to carcinogenic and mutagenic agents,” A. Berlin, M. Draper, K. Hemminki, H. Vainio, eds., International Agency for Research on Cancer, Lyon.Google Scholar
  3. Ashby, J., 1988, Comparison of techniques for monitoring human exposure to genotoxic chemicals, Mutat. Res. 204: 543.PubMedCrossRefGoogle Scholar
  4. Brothman, A. R., Davis, T. P., Duffy, J. J., and Lindell, T. J., 1982, Development of an antibody to actinomycin D and its application for the detection of serum levels by radioimmunoassay, Cancer Res., 42: 1184.PubMedGoogle Scholar
  5. Caviezel, M., Aeschbach, A. P., Lutz, W. K., and Schlatter, C., 1984, Reduction of covalent binding of aflatoxin B1 to rabbit liver DNA after immunization against this carcinogen, Arch. Toxicol., Supp1. 7: 249.CrossRefGoogle Scholar
  6. Creech, H. J., 1952, Chemical and immunological properties of carcinogen-protein conjugates. Cancer Res. 12: 557.PubMedGoogle Scholar
  7. Dragsted, L. O., Bull, I., and Autrup, H., 1988, Substances with affinity to a monoclonal aflatoxin B1 antibody in Danish urine samples, Fd. Chem. Toxic. 26: 233.CrossRefGoogle Scholar
  8. Eggset, G., Volden, G., and Krokan, H., 1983, U.v.-induced DNA damage and its repair in human skin in vivo studied by sensitive immunohistochemical methods, Carcinog. 4: 745.CrossRefGoogle Scholar
  9. Erlanger, B., and Beiser, S., 1964, Antibodies specific for ribonucleosides, ribonucleotides and their reaction with DNA, Proc. Natl. Acad. Sci. USA, 52: 68PubMedCrossRefGoogle Scholar
  10. Fan, T. S. L., Zhang, G. S., and Chu, F. S., 1984, Production and characterisation of antibody against aflatoxin Q1, Appl. Environ. Microbiol. 47: 526.PubMedGoogle Scholar
  11. Farmer, P. B., Neumann, H.-G., and Henschler, D., 1987, Estimation of exposure of man to substances reacting covalently with macromolecules, Arch Toxicol 60: 251.PubMedCrossRefGoogle Scholar
  12. Foiles, P. G., Truschin, N., and Castonguay, A., 1985, Measurement of 06-methyldeoxyguanosine in DNA methylated by the tobacco-specific carcinogen 4-(methylnitrosamino)1-(3-pyridyl)-l-butanone using a biotin-avidin enzyme-linked immunosorbent assay, carcinogenesis 6: 989.PubMedCrossRefGoogle Scholar
  13. Fujiwara, K., Saikusa, H., Yasuno, M., and Kitagawa, T., 1982, Enzyme immunoassay for the quantification of mitomycin C using B-galactosidase as a label, Cancer Res., 42: 1487.PubMedGoogle Scholar
  14. Groopman, J.D., Trudel, L.J., Donahue, P.R., MarshakRothstein, A., and Wogan, G.N., 1984, High-affinity monoclonal antibodies for aflatoxins and their application to solid-phase immunoassays, Proc. Natl. Acad., 81: 7728.CrossRefGoogle Scholar
  15. Groopman, J. D., Donahue, P.R., Zhu, J., Chen, J., and Wogan, G. N., 1985, Aflatoxin metabolism in humans: Detection of metabolites and nucleic acid adducts in urine by affinity chromatography, Proc. Natl. Acad. Sci. 82: 6492.PubMedCrossRefGoogle Scholar
  16. Harris, C. C., Vähäkangas, K., Newman, M. J., 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. 82: 6672.PubMedCrossRefGoogle Scholar
  17. Haugen, Aa., Becher, G., Benestad, C., Vähäkangas, K., Trivers, G. E., Newman, M. J., and Harris, C. C., 1986, Determination of polycyclic aromatic hydrocarbons in the urine, benzo[a]pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amounts of polycyclic aromatic hydrocarbons in the work atmosphere, Cancer Res. 46: 4178.PubMedGoogle Scholar
  18. Haugen, AA., Groopman, J.D., Hsu, I-C., Goodrich, G.R., Wogan, and Harris, C.C., 1981, Monoclonal antibody to aflatoxin B1-modified DNA detected by enzyme immunoassay, Proc. Natl. Acad. Sci., 78: 4124.PubMedCrossRefGoogle Scholar
  19. Hertzog, P. J., Lindsay Smith, J. R., and Garner, R. C., 1982, Production of monoclonal antibodies to guanine opened aflatoxin B1 DNA, the persistent DNA adduct in vivo, Carcinog., 3: 825.CrossRefGoogle Scholar
  20. Hsu, I.C., Poirier, M.C., Yuspa, S.H., Yolken, R.H., and C.C. Harris, 1980, Ultrasensitive enzymatic radioimmunoassay (USERIA) detects femtomoles of acetylaminofluorene-DNA adducts, Carcinog. 1: 455.CrossRefGoogle Scholar
  21. Hsu, I-C., Poirier, M. C., Yuspa, S. H., Grunberger, D., Weinstein, I. B., Yolken, R. H., and Harris, C. C., 1981, Measurement of benzo[a]pyrene-DNA adducts by enzyme immunoassays and radioimmunoassay, Cancer Res., 41: 1091.PubMedGoogle Scholar
  22. Johnson, H. J., Jr., Cemosek, S. F.,Jr., Gutierrez-Cemosek, R. M., and Brown, L. L., 1980, Development of a radioimmunoassay procedure for 4-acetamidobiphenyl, a metabolite of the chemical carcinogen 4-aminobiphenyl, in urine, J. of Anal. Tox. 4: 86.Google Scholar
  23. Kriek, E., Engelse, L. D., Scherer, E., and Westra, G., 1984, Formation of DNA modifications by chemical carcinogens identification, localisation and quantification, Biochim. Biophvs. Acta 738: 181.Google Scholar
  24. Leng, M., Sage, E., Fuchs, R. P., and Daune, M. P., 1978, Antibodies to DNA modified by the carcinogen, N-acetoxyN-2-acetylaminofluorene, FEBS Lett., 92: 207.PubMedCrossRefGoogle Scholar
  25. Malfoy, B., Hartmann, B., Macquet, J-P., and Leng, M., 1981, Immunochemical studies of DNA modified by cis-dichlorodiammineplatinum(II) in vivo and in vitro, Cancer Res. 41: 4127.PubMedGoogle Scholar
  26. Martin, C. N., Garner, R. C., Tursi, F., Garner, J. V., Whittle, H. C., Sizaret, R. P., and Montesano, R., 1984, An elisa Procedure for assaying aflatoxin B1, in Berlin, A., Draper, M., Hemminki, K. & Vainio, H. eds. Monitoring Human Exposure to Carcinogenic and Mutagenic Agents (IARC Scientific Publications No. 59 ), International Agency for Research on Cancer, Lyon.Google Scholar
  27. Menkveld, G. J., Van Der Laken, C. J., Hermsen, T., Kriek, E., Scherer, E., and Den Engelse, L., 1985, Immunohistochemical localisation of 06-ethyldeoxyguanosine and deoxyguanosin-8-y1-(acetyl)aminofluorene in liver sections of rats treated with diethylnitrosamine, ethylnitrosourea or N-acetylaminofluorene, Carcinog. 6: 263.CrossRefGoogle Scholar
  28. Moolten, F. L., Schreiber, B., Rizzone, A., Weiss, A. J., and Boger, E., 1981, Protection of mice against 7,12-dimethylbenz[a]anthracene-induced skin tumors by immunization with afluorinated analog of the carcinogen, Cancer Res, 41: 425.PubMedGoogle Scholar
  29. Moss, E. J., and Neal, G. E., 1985, The metabolism of aflatoxin B1 by human liver, Biochem. Pharmacol. 34: 3193.PubMedCrossRefGoogle Scholar
  30. Müller, R., and Rajewsky, M.R., 1980, Immunological quantification by high-affinity antibodies of 06-ethyldeoxyguanosine in DNA exposed to N-ethyl-N-nitrosourea, Cancer Res. 40: 887.PubMedGoogle Scholar
  31. Nehls, P.,Adamkiewicz, J., and Rajewsky, M. F., 1984, ImmunoSlot-Blot: A highly sensitive immunoassay for the quantitation of carcinogen-modified nucleosides in DNA, J. Cancer Res. Clin. Oncol. 108: 23.PubMedCrossRefGoogle Scholar
  32. Osterman-Golkar, S., Hultmark, D., Segerbäck, D., Calleman, C. J., Gothe, R., Ehrenberg, L., and Wachtmeister, C. A., 1977, Alkylation of DNA and proteins in mice exposed to vinyl chloride, Biochem. Biophys. Res. Commun. 76: 259.CrossRefGoogle Scholar
  33. Perera, F. P., Santella, R. M., and Poirier, M. C., 1985, Potential methods to monitor human populations exposed to carcinogens: Carcinogen-Dna binding as an example, in: “Risk quantitation and regulatory policy,” D. G. Hoel, R. A. Merrill, F. P. Perera, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor.Google Scholar
  34. Perera, F. P., 1987, Molecular Cancer Epidemiology: A new tool in cancer prevention, JNCI 78: 887.PubMedGoogle Scholar
  35. Pestka, J. J., Li, Y. K., and Chu, F. S., 1982, Reactivity of aflatoxin B2a antibody with aflatoxin B1-modified DNA and related metabolites, Appl. Environ. Microbiol. 44: 1159.PubMedGoogle Scholar
  36. Pestka, J. J., and Chu, F. S., 1984, Aflatoxin B1 dihydrodiol antibody: Production and specificity, AApl. Environ. Microbiol. 47: 472.Google Scholar
  37. Plooy, A.C.M., van Dijk, M., and Lohman, P.H.M., 1984, Induction and repair of DNA cross-links in Chinese hamster ovary cells treated with various platinum coordination compounds in relation to platinum binding to DNA, cytotoxicity, Cancer Res. 44: 2043.PubMedGoogle Scholar
  38. Plooy, A. C. M., Fichtinger-Schepman, A. M. J.., Schutte, H. H., van Dijk, M., and Lohman, P. H. M., 1985, The quantitative detection of various Pt-DNA-adducts in Chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques, Carcinoq. 6: 561.CrossRefGoogle Scholar
  39. Poirier, M. C., Yuspa, S. H., Weinstein, I. B., and Blobstein, S., 1977, Detection of carcinogen-DNA adducts by radio-immunoassay Nature, 270: 186.PubMedCrossRefGoogle Scholar
  40. Poirier, M.C., Santella, R., Weinstein, I.B., Grunberger, D., and Yuspa, S. H., 1980, Quantitation of Benzo(a)pyrenedeoxyguanosine adducts by radioimmunoassay, Cancer Res. 40: 412.PubMedGoogle Scholar
  41. Poirier, M.C., 1981, Antibodies to carcinogen-DNA adducts, JNCI, 67: 515.PubMedGoogle Scholar
  42. Poirier, M.C., M.C., Lippard, S.J., Zwelling, L.A., Ushay, H.M., Kerrigan, D., Thill, C.C., Santella, R.M., Grunberger, D., and Yuspa, S.H., 1982, Antibodies elicited against cisdiamminedichloroplatinum(II)-modified DNA are specific for cis-diamminedichloro-platinum(II)-DNA adducts formed in vivo and in vitro, Proc. Natl. Acad. Sci. 79: 6443.Google Scholar
  43. Poirier, M. C., 1984, The use of carcinogen-DNA adduct antisera for quantitation and localisation of genomic damage in animal and the human population, Environ. Mutagen. 6: 879.PubMedCrossRefGoogle Scholar
  44. Poirier, M. C., Reed, E., Zwelling, L. A., Ozols, R. F., Litterst, C. L., and Yuspa, S. H., 1985, Polyclonal antibodies to quantitate cis-diamminedichloroplatinum(II)-DNA adducts in cancer patients and animal models, Environ. Hlth. Perspect. 62: 89Google Scholar
  45. Rajewsky, M. F., Müller, R., Adamkiewicz, J., and Drosdziok, W., 1980, Immunological detection and quantification of DNA components structurally modified by alkylating carcinogens (ethylnitrosourea), In: B. Pullman, P. O. P. Tso, H. Gelboin, eds., Carcinogenesis: Fundamental mechanisms and environmental effects, Reidel, Dordrecht.Google Scholar
  46. Reed, E., Yuspa, S. H., Zwelling, L. A., Ozols, R. F., and Poirier, M. C., 1986, Quantitation of cis-Diamminedichloroplatinum II (Cisplatìn)-DNA-Intrastrand adducts in testicular and ovarian cancer patients receiving cisplatin chemotherapy, J. Clin. Invest. 77: 545.PubMedCrossRefGoogle Scholar
  47. Safhill, R., Strickland, P. T., and Boyle, J. M., 1982, Sensitive radioimmunoassays for 06-n-butyldeoxyguanosine, 02- n-butylthymídine and 04-n-butylthymidine, carcinogenesis 5: 547.CrossRefGoogle Scholar
  48. Santella, R.M., Lin, C.D., Cleveland, W.L., and Weinstein, I.B., 1984, Monoclonal antibodies to DNA modified by a benzo[a]pyrene diol epoxide, Carcinogenesis 5: 373.PubMedCrossRefGoogle Scholar
  49. Santella, R. M., Lin, C. D., and Dharmaraja, N., 1986, Monoclonal antibodies to a benzo[a]pyrene diolepoxide modified protein, Carcinogenesis 7: 441.PubMedCrossRefGoogle Scholar
  50. Segerbäck, D., 1983, Alkylation of DNA and hemoglobin in the mouse following exposure to ethene and ethene oxide, Chem. Biol Interact 45: 139.PubMedCrossRefGoogle Scholar
  51. Sizaret, P., Malaveille, C., Montesano R., and Frayssinet, 1982, Detection of aflatoxins and related metabolites by radioimmunoassay, JNCI 69: 1375.PubMedGoogle Scholar
  52. Strickland, P. T., and Boyle, J.M., 1984, Immunoassay of carcinogen modified DNA, Prog. Nucleic Acid Res. Mol. Biol. 31: 1.PubMedCrossRefGoogle Scholar
  53. Sun, T., Wu Y., and Wu, S., 1983, Monoclonal antibody against aflatoxin B1, and its potential applications, Chinese J. Oncol., 5: 401.Google Scholar
  54. Tsuboi, S., Nakagawa, T., Tornita, M., Seo, T., Ono, H., Kawamura, K., and Iwamura, N., 1984, Detection of Aflatoxin B1 in Serum Samples of Male Japanese Subjects by Radioimmunoassay and High-Performance Liquid Chromatography, Cancer Res. 44: 1231.PubMedGoogle Scholar
  55. Umbenhauer, D., Wild, C.P., Montesano, R., Saffhill, R., Boyle, J.M., Huh, N., Kirstein, U., Thomale, J., Rajewsky, M.F. and Lu, S.H., 1985, 06-Methyldeoxyguanosine in Oesophageal DNA among individuals at high risk of Oesophageal cancer, Int. J. Cancer 36:661.Google Scholar
  56. Vanderlaan, M., Watkins, B.E., Hwang, M., Knize, M. G., and Felton, J.S., 1988, Monoclonal antibodies for the immunoassay of mutagenic compounds produced by cooking beef, Carcinog. 9: 153.CrossRefGoogle Scholar
  57. Van der Laken, C. J., Hagenaars, A. M., Hermsen, G., Kriek, E., Kuipers, A. J., Nagel, J., Scherer, E., and Welling, M., 1982, Measurement of 06-ethyldeoxyguanosine and N(deoxyguanosin-8-yl)-N-acetyl-aminofluorene in DNA by high-sensitivity enzyme immunoassays, carcinogenesis 5: 569.CrossRefGoogle Scholar
  58. Vainio, H., 1985, Current trends in the biological monitoring of exposure to carcinogens, Scand J Work Environ Health 11: 1PubMedCrossRefGoogle Scholar
  59. Wani, A. A., Gibson-D’Ambrosio, R. E., and D’Ambrosio, S. M., 1984, Quantitation of 06-ethyldeoxyguanosine in ENU alkylated DNA by polyclonal and monoclonal antibodies, Carcinoq. 5: 1145.CrossRefGoogle Scholar
  60. Wild, C. P., Smart, G., Saffhill, R., and Boyle, J. M., 1983, Radioimmunoassay of 06-methyldeoxyguanosine in DNA of cells alkylated in vitro and in vivo, Carcinog. 4: 1605.CrossRefGoogle Scholar
  61. Wild, C. P., Umbernhauer, D., Chapot, B., and Montesano, R., 1986, Monitoring of individual human exposure to aflatoxins (AF) and N-Nitrosamines (NNO) by immunoassays, J. Cell. Biochem., 30: 171.PubMedCrossRefGoogle Scholar
  62. Woychik, N. A., Hinsdill, R. D., and Chu, F. S., 1984, Production and characterisation of monoclonal antibodies Against aflatoxin M1, Appl. Environ. Microbiol., 48:1096.Google Scholar
  63. Yang, G., Nesheim, S., Benavides, J., Ueno, I., Campbell, A. D., and Poland, A., 1980, Radioimmunoassay detection of Aflatoxin B1 in monkey and human urine, Medical Mycology, Zbl. Bakt. suppl. 8: 329.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Lars O. Dragsted
    • 1
  1. 1.Department of Biochemical and Molecular ToxicologyNational Food Agency of Denmark, Institute of ToxicologySøborgDenmark

Personalised recommendations