Advertisement

Carcinogen-DNA and Protein Adducts as Intermediate Biomarkers for Human Chemoprotection Trials

  • John D. Groopman
  • Bill D. Roebuck
  • Thomas W. Kensler
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 375)

Abstract

Our rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from carcinogen exposure through clinical cancer. A joint committee of the National Academy of Sciences and the National Research Council1 has developed a useful conceptual framework for these processes and is shown in an adapted form in Figure 1. This model groups molecular biomarkers into sets reflective of internal dose, biologically effective dose (dose to critical macromolecules), early biological effect, altered structure/function, and clinical disease as well as those reflecting underlying susceptibility factors. In more general terms, molecular biological markers can be considered to fall into broad categories of markers of exposure, biological effect, and susceptibility. Markers of exposure reflect exposure levels to toxic agents, markers of effect indicate a biological response to an exposure, and markers of susceptibility provide information about the inherent sensitivity of an individual to a toxic agent. By definition some of these markers are chemical-agent specific, such as a carcinogen-DNA or protein adduct, while others are biological-process specific, such as the altered expression of an oncogene protein.

Keywords

Liver Cancer Protein Adduct Intermediate Endpoint Aflatoxin Exposure Chemoprotective Agent 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    National Research Council Committee on Biological Markers, Biological markers in environmental health research, Env Hlth Persp 74:3–9 (1987).Google Scholar
  2. 2.
    W.F. Busby, G.N. Wogan, Aflatoxins, in: Chemical Carcinogens, 2nd Ed., C.E. Searle, ed., pp. 945–1136, American Chemical Society, Washington, D.C. (1985).Google Scholar
  3. 3.
    J.D. Groopman, G. Sabbioni, C.P. Wild, Molecular dosimetry of aflatoxin exposures, in: Molecular Dosimetry of Human Cancer: Epidemiological, Analytical and Social Considerations, J.D. Groopman, P. Skipper, eds., pp. 302–324, CRC Press, Boca Raton, FL (1991).Google Scholar
  4. 4.
    B. Hulka, Epidemiological studies using biological markers: Issues for epidemiologists, Cancer Epidemiology, Biomarkers and Prevention 1:13–19 (1991).PubMedGoogle Scholar
  5. 5.
    J.M. Essigmann, R.G. Croy, A.M. Nadzan, W.F. Busby, Jr., V.N. Reinhold, G. Buchi, G.N. Wogan, Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro, Proc Natl Acad Sci USA 74:1870–1874 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    G. Sabbioni, P. Skipper, G. Buchi, S.R. Tannenbaum, Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1 in vivo in rats, Carcinogenesis 8:819–824 (1987).PubMedCrossRefGoogle Scholar
  7. 7.
    S. Appleton, M.P. Goetchius, T.C. Campbell, Linear dose-response curve for hepatic macromolecular binding of aflatoxin B1 in rats at very low exposures, Cancer Res 42:3659–3662 (1982).PubMedGoogle Scholar
  8. 8.
    C.P. Wild, R.G. Garner, R. Montesano, F. Tursi, Aflatoxin B1 binding to plasma albumin and liver DNA upon chronic administration to rats, Carcinogenesis 7:853–858 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    J.D. Groopman, W.F. Busby, G.N. Wogan, The nuclear distribution of aflatoxin B1 and its interaction with histones in vivo, Cancer Res 40:4343–4351 (1980).PubMedGoogle Scholar
  10. 10.
    R.A. Bennett, J.M. Essigmann, G.N. Wogan, Excretion of an aflatoxin-guanine adduct in the urine of aflatoxin B1-treated rats, Cancer Res 41:650–654 (1981).PubMedGoogle Scholar
  11. 11.
    J.D. Groopman, J. Hasler, L.J. Trudel, A. Pikul, P.R. Donahue, G.N. Wogan, Molecular dosimetry in rat urine of aflatoxin-N 7-guanine and other aflatoxin metabolites by multiple monoclonal antibody affinity chromatography and HPLC, Cancer Res 52:267–27A (1992).PubMedGoogle Scholar
  12. 12.
    R.G. Croy, G.N. Wogan, Temporal patterns of covalent DNA adduets in rat liver after single and multiple doses of aflatoxin B1 Cancer Res 41:197–203 (1981).PubMedGoogle Scholar
  13. 13.
    D.E. Goeger, D. Shelton, J.D. Hendricks, C. Pereira, G.S. Bailey, Comparative effect of dietary butylated hydroxyanisole and β-naphthoflavone on aflatoxin B1 metabolism, DNA adduct formation and carcinogenesis in rainbow trout, Carcinogenesis 9:1793–1800 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    T.W. Kensler, P.A. Egner, N.E. Davidson, B.D. Roebuck, A. Pikul, J.D. Groopman, Modulation of aflatoxin metabolism, aflatoxin-N 7-guanine formation, and hepatic tumorigenesis in rats fed ethoxyquin: Role of induction of glutathione S-transferase, Cancer Res 46:3924–3931 (1986).PubMedGoogle Scholar
  15. 15.
    H. Autrup, K.A. Bradley, A.K.M. Shamsuddin, J. Wakhisi, A. Wasunna, Detection of putative adduct with fluroescence characteristics identical to 2,3-dihydro-2-(7′-guanyl)-3-hydroxyaflatoxin Bl in human urine collected in Murang’a district, Kenya, Carcinogenesis 4:1193–1195 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    H. Autrup, T. Seremet, J. Wakhisi, A. Wasunna, Aflatoxin exposure measured by urinary excretion of aflatoxin B1-guanine adduct and hepatitis B virus infection in areas with different liver cancer incidence in Kenya, Cancer Res 47:3430–3433 (1987).PubMedGoogle Scholar
  17. 17.
    J.D. Groopman, J. Zhu, P.R. Donahue, A. Pikul, L.-S. Zhang, J.-S. Chen, G.N. Wogan, Molecular dosimetry of urinary aflatoxin DNA adducts in people living in Guangxi Autonomous Region, People’s Republic of China, Cancer Res 52:45–51 (1992).PubMedGoogle Scholar
  18. 18.
    L.-S. Gan, PL. Skipper, X.-C. Peng, J.D. Groopman, J.-S. Chen, G.N. Wogan, S.R. Tannenbaum, Serum albumin adducts in the molecular epidemiology of aflatoxin carcinogenesis: Correlation with aflatoxin B1 intake and urinary excretion of aflatoxin M1, Carcinogenesis 9:1323–1325 (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    J.D. Groopman, A. Hall, H. Whittle, G. Hudson, G.N. Wogan, R. Montesano, C.P. Wild, Molecular dosimetry of aflatoxin-N 7-guanine in human urine obtained in The Gambia, West Africa, Cancer Epidemiology, Biomarkers and Prevention 1:221–228 (1992).PubMedGoogle Scholar
  20. 20.
    C.P. Wild, G. Hudson, G. Sabbioni, G.N. Wogan, H. Whittle, R. Montesano, J.D. Groopman, Correlation of dietary intake of aflatoxins with the level of albumin bound aflatoxin in peripheral blood in The Gambia, West Africa, Cancer Epidemiology, Biomarkers and Prevention 1:229–234 (1992).PubMedGoogle Scholar
  21. 21.
    C.P. Wild, Y.Z. Jiang, G. Sabbioni, B. Chapot, R. Montesano, Evaluation of methods for quantitation of aflatoxin-albumin adducts and their application to human exposure assessment, Cancer Res 50:245–251 (1990).PubMedGoogle Scholar
  22. 22.
    C.P. Wild, Y.Z. Jiang, S.J. Allen, L.A. Jansen, A.J. Hall, R. Montesano, Aflatoxin-albumin adducts in human sera from different regions of the world, Carcinogenesis 11:2271–2274 (1990).PubMedCrossRefGoogle Scholar
  23. 23.
    T.C. Campbell, J. Chen, C. Liu, J. Li, B. Parpia, Nonassociation of aflatoxin with primary liver cancer in a cross-sectional ecological survey in the People’s Republic of China, Cancer Res 50:6881–6893 (1990).Google Scholar
  24. 24.
    P. Srivatanakul, D.M. Parkin, M. Khlat, D. Chenvidhya, P. Chotiwan, S. Insiripong, K.A. L’Abbe, C.P. Wild, Liver cancer in Thailand. II. A case-control study of hepatocellular carcinoma, Int J Cancer 48:329–332 (1991).PubMedCrossRefGoogle Scholar
  25. 25.
    R. Ross, J.-M. Yuan, M. Yu, G.N. Wogan, G.-S. Qian, J.-T. Tu, J.D. Groopman, Y.-T. Gao, B.E. Henderson, Urinary aflatoxin in biomarkers and risk of hepatocellular carcinoma, The Lancet 339:943–946 (1992).CrossRefGoogle Scholar
  26. 26.
    J.R. Cabrai, G.E. Neal, The inhibitory effects of ethoxyquin on the carcinogenic action of aflatoxin B1 in rats, Cancer Lett 19:125–132 (1983).CrossRefGoogle Scholar
  27. 27.
    G.M. Williams, T. Tanaka, Y. Maeura, Dose-related inhibition of aflatoxin B1-indueed hepatocarcinogenesis by the phenolic antioxidants butylated hydroxytoluene and butylated hydroxyanisole, Carcinogenesis 7:1043–1046 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    T.W. Kensler, P.A. Egner, M.A. Trush, E. Bueding, J.D. Groopman, Modification of aflatoxin B1 binding to DNA in vivo in rats fed phenolic antioxidants, ethoxyquin, and a dithiothione, Carcinogenesis 6:759–764 (1985).PubMedCrossRefGoogle Scholar
  29. 29.
    T.W. Kensler, P.A. Egner, PH. Dolan, J.D. Groopman, B.D. Roebuck, Mechanism of protection against aflatoxin tumorigenesis in rats fed oltipraz and related 1,2-dithiol-3-thiones and 1,2-dithiol-3-ones, Cancer Res 47:4271–4277 (1987).PubMedGoogle Scholar
  30. 30.
    B.D. Roebuck, Y.-L. Liu, A.E. Rogers, J.D. Groopman, T.W. Kensler, Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz): Predictive role for short-term molecular dosimetry, Cancer Res 51:5501–5506 (1991).PubMedGoogle Scholar
  31. 31.
    Y.-L. Liu, B.D. Roebuck, J.D. Yager, J.D. Groopman, T.W. Kensler, Protection by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) against the hepatotoxicity of aflatoxin B1 in the rat, Toxicol Appl Pharmacol 93:442–451 (1988).PubMedCrossRefGoogle Scholar
  32. 32.
    T.W. Kensler, J.D. Groopman, D.L. Eaton, T.J. Curphey, B.D. Roebuck, Potent inhibition of aflatoxin-induced hepatic tumorigenesis by the monofunctional enzyme inducer 1,2-dithiole-3-thione, Carcinogenesis 12:95–100 (1992).CrossRefGoogle Scholar
  33. 33.
    R.G. Croy, J.M. Essigmann, V.N. Reinhold, G.N. Wogan, Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver, Proc Natl Acad Sci USA 75:1745–1749 (1978).PubMedCrossRefGoogle Scholar
  34. 34.
    S.M. Lippman, J.S. Lee, R. Lotan, W. Hittleman, M.J. Wargovich, W.K. Hong, Biomarkers as intermediate end points in chemoprevention trials, J Natl Cancer Inst 82:555–562 (1990).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • John D. Groopman
    • 1
  • Bill D. Roebuck
    • 2
  • Thomas W. Kensler
    • 1
  1. 1.Department of Environmental Health SciencesThe Johns Hopkins University School of Hygiene and Public HealthBaltimoreUSA
  2. 2.Department of Pharmacology and ToxicologyDartmouth Medical SchoolHanoverUSA

Personalised recommendations