Skip to main content

High-Affinity Monoclonal Antibodies Specific for Deoxynucleosides Structurally Modified by Alkylating Agents: Applications for Immunoanalysis

  • Conference paper
Book cover Biological Dosimetry

Abstract

Mutagenic and carcinogenic chemicals, most cancer chemotherapeutic agents, as well as ionizing radiation and ultraviolet light, cause structural alterations of DNA in the chromatin of target cells (see Town et al. 1973; Lawley 1976; Wang 1976; Grover 1979; Rajewsky 1980; Waring 1981; Singer and Kuśmierek 1982). In the case of alkylating chemical agents, covalent binding generally occurs between nucleophilic centers (electron-rich N and О atoms) in DNA and strongly reactive, electrophilic derivatives, generated from the respective parent compounds either enzymatically (“metabolic activation”) or via non-enzymatic decomposition (see Magee 1974; Miller and Miller 1979, 1981; Gelboin 1980). As for most of the DNA alterations caused by various types of radiation, the precise structure of many chemical DNA adducts remains to be elucidated. Nevertheless, several classes of DNA-reactive chemicals have already been very thoroughly studied with regard to their DNA binding products, and in relation to the potential consequences of these DNA adducts in terms of cytotoxicity, mutagenesis, or malignant transformation. Thus, the various types of structural modifications of DNA resulting from the exposure of cells to alkylating N-nitroso compounds (alkylnitrosoureas, al-kylnitrosoamines, alkylnitro-nitroso-guanidines) have for the most part been identified (Lawley 1976; Grover 1979; Singer 1979; Rajewsky 1980, 1983).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adamkiewicz J, Drosdziok W, Eberhardt W, Langenberg U, Rajewsky MF (1982) High-affinity monoclonal antibodies specific for DNA components structurally modified by alkylating agents. In: Bridges BA, Butterworth BE, Weinstein IB (eds) Indicators of genotoxic exposure. Banbury Report 13. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 265–276

    Google Scholar 

  • Adamkiewicz J, Ahrens O, Huh N, Rajewsky MF (1983) Quantitation of alkyl-deoxynucleosides in the DNA of individual cells by high-affinity monoclonal antibodies and electronically intensified, direct immunofluorescence. J Cancer Res Clin Oncol 105: A15

    Google Scholar 

  • Baird WM (1979) The use of radioactive carcinogens to detect DNA modification. In: Grover PL (ed) Chemical carcinogens and DNA. CRC Press, Boca Raton, pp 59–83

    Google Scholar 

  • Beiser SM, Tanenbaum SW, Erlanger BF (1968) Purine- and pyrimidine-protein conjugates. Meth Enzymol 12:889–893

    Article  CAS  Google Scholar 

  • Beranek DT, Weis CC, Swenson DH (1980) A comprehensive quantitative analysis of methylated and ethylated DNA using high pressure liquid chromatography. Carcinogenesis 1:595–606

    Article  PubMed  CAS  Google Scholar 

  • Briscoe WT, Spizizen J, Tan EM (1978) Immunological detection of O6-methylguanine in alkylated DNA. Biochemistry 17:1896–1901

    Article  PubMed  CAS  Google Scholar 

  • DeMurcia G, Lang MCE, Freund AM, Fuchs RPP, Daune MP, Sage E, Leng M (1979) Electron microscopic visualization of N-aeetoxy-N-2-acetylaminofluorene binding sites in Col E-1 DNA by means of specific antibodies. Proc Natl Acad Sci USA 76:6076–6080

    Article  CAS  Google Scholar 

  • Druckrey H (1971) Genotypes and phenotypes of ten inbred strains of BD-rats. Arzneim Forsch 21: 1274–1278

    CAS  Google Scholar 

  • Erlanger BF (1973) Principles and methods for the preparation of drug-protein conjugates for immunological studies. Pharmacol Rev 25:271–280

    PubMed  CAS  Google Scholar 

  • Erlanger BF, Beiser SM (1964) Antibodies specific for ribonucleosides and ribonucleotides and their reaction with DNA. Proc Natl Acad Sci USA 52:68–74

    Article  PubMed  CAS  Google Scholar 

  • Farr RS (1958) A quantitative immunological measure of the primary interaction between I BSA and antibody. J Infect Dis 103:239–262

    Article  PubMed  CAS  Google Scholar 

  • Galfré G, Milstein C, Wright B (1979) Rat x rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG. Nature 277:131–133

    Article  PubMed  Google Scholar 

  • Gelboin HV (1980) Benzo[a]pyrene metabolism, activation, and carcinogenesis: Role and regulation of mixed-function oxidases and related enzymes. Physiol Rev 60:1107–1166

    PubMed  CAS  Google Scholar 

  • Goth R, Rajewsky MF (1974) Molecular and cellular mechanisms associated with pulse-carcinogenesis in the rat nervous system by ethylnitrosourea: ethylation of nucleic acids and elimination rates of ethylated bases from the DNA of different tissues. Z Krebsforsch 82:37–64

    Article  CAS  Google Scholar 

  • Grabar P, Avrameas S, Taudou B, Salomon JC (1968) Formation and isolation of antibodies specific for nucleosides. In: Plescia OJ, Braun W (eds) Nucleic acids in immunology. Springer, Berlin New York, pp 79–87

    Google Scholar 

  • Groopman JD, Haugen Å, Goodrich GR, Wogan GN, Harris CC (1982) Quantitation of aflatoxin B1-modified DNA using monoclonal antibodies. Cancer Res 42:3120–3124

    PubMed  CAS  Google Scholar 

  • Grover PL (ed) (1979) Chemical carcinogens and DNA, Vol I and II. CRC Press, Boca Raton

    Google Scholar 

  • Gupta RC, Reddy MV, Randerath K (1982) 32P.postlabeling analysis of non-radioactive aromatic carcinogen-DNA adducts. Carcinogenesis 3:1081–1092

    Article  PubMed  CAS  Google Scholar 

  • Halloran MJ, Parker CW (1966) The preparation of nucleotide-protein conjugates: Carbodiimides as coupling agents. J Immunol 96:373–378

    PubMed  CAS  Google Scholar 

  • Haugen Å, Groopman JD, Hsu IC, Goodrich GR, Wogan JN, Harris CC (1981) Monoclonal antibody to aflatoxin B1-modified DNA detected by enzyme immunoassay. Proc Natl Acad Sci USA 78: 4124–4127

    Article  PubMed  CAS  Google Scholar 

  • Hsu IC, Pokier MC, Yuspa SH, Yolken RH, Harris CC (1980) Ultrasensitive enzymatic radioimmunoassay (USERIA) detects femtomoles of acetylaminofluorene-DNA adducts. Carcinogenesis 1:455–458

    Article  PubMed  CAS  Google Scholar 

  • Hsu IC, Poirier MC, Yuspa SH, Grunberger D, Weinstein IB, Yolken RH, Harris CC (1981) Measurement of benzo(a)pyrene-DNA adducts by enzyme immunoassay and radioimmunoassay. Cancer Res 41:1091–1095

    PubMed  CAS  Google Scholar 

  • Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497

    Article  PubMed  Google Scholar 

  • Kriek E, van der Laken CJ, Welling M, Nagel J (1982) Immunological detection and quantification of the reaction products of 2-acetylaminofluorene with guanine in DNA. In: Bartsch H, Armstrong B (eds) Host factors in human carcinogenesis. IARC Scientific Publications No 39. International Agency for Research on Cancer, Lyon, pp 541–549

    Google Scholar 

  • Kyrtopoulos SA, Swann PF (1980) The use of radioimmunoassay to study the formation and disappearance of O6-methylguanine in mouse liver satellite and main-band DNA following dimethyl-nitrosamine administration. J Cancer Res Clin Oncol 98:127–138

    Article  PubMed  CAS  Google Scholar 

  • Lawley PD (1976) Carcinogenesis by alkylating agents. In: Searle CE (ed) Chemical carcinogens. ACS Monograph No 173. American Chemical Society, Washington, D.C., pp 83–244

    Google Scholar 

  • Leng M, Sage E, Fuchs RPP, Daune MP (1978) Antibodies to DNA modified by the carcinogen N-acetoxy-N-2-acetylaminofluorene. FEBS Lett 92:207–210

    Article  PubMed  CAS  Google Scholar 

  • Lo KM, Franklin WA, Lippke JA, Henner WD, Haseltine WA (1982) New methods for the detection of DNA damage to human cellular DNA by envkonmental carcinogens and anti-tumor drugs. In: Bridges BA, Butterworth BE, Weinstein IB (eds) Indicators of genotoxic exposure, Banbury Report 13. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 253–263

    Google Scholar 

  • Magee PN (1974) Activation and inactivation of chemical carcinogens and mutagens in the mammal. In: Campbell PN, Dickens F (eds) Essays in biochemistry, Vol 10. Academic Press, London, pp 105–136

    Google Scholar 

  • Meredith RD, Erlanger BF (1979) Isolation and characterization of rabbit anti-m7G-5′-P antibodies of high apparent affinity. Nucleic Acids Res 6:2179–2191

    Article  PubMed  CAS  Google Scholar 

  • Miller EC, Miller JA (1981) In search of ultimate chemical carcinogens and their reactions with cellular macro molecules. In: Fortner JG, Rhoads JE (eds) Accomplishments in cancer research 1980. Lippincott JB, Philadelphia, pp 63–98

    Google Scholar 

  • Miller JA, Miller EC (1979) Perspectives on the metabolism of chemical carcinogens. In: Emmelot P, Kriek E (eds) Environmental carcinogenesis. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 25–50

    Google Scholar 

  • Müller R (1980) Calculation of average antibody affinity in anti-hapten sera from data obtained by competitive radioimmunoassay. J Immunol Meth 34:345–352

    Article  Google Scholar 

  • Müller R, Rajewsky MF (1978) Sensitive radioimmunoassay for detection of O6-ethyldeoxyguanosine in DNA exposed to the carcinogen ethylnitrosourea in vivo or in vitro. Z Naturforsch 33c: 897–901

    Google Scholar 

  • Müller R, Rajewsky MF (1980) Immunological quantification by high affinity antibodies of O6-ethyl-deoxyguanosine in DNA exposed to N-ethyl-N-nitrosourea. Cancer Res 40:887–896

    PubMed  Google Scholar 

  • Müller R, Rajewsky MF (1981) Antibodies specific for DNA components structurally modified by chemical carcinogens. J Cancer Res Clin Oncol 102:99–113

    Article  PubMed  Google Scholar 

  • Müller R, Adamkiewicz J, Rajewsky MF (1982) Immunological detection and quantification of carcinogen-modified DNA components. In: Bartsch H, Armstrong B (eds) Host factors in human carcinogenesis. IARC Scientific Publications No 39. International Agency for Research on Cancer, Lyon, pp 463–479

    Google Scholar 

  • Nehls P, Spiess E, Rajewsky MF (1983) Visualization of O6-ethylguanine in ethylnitrosourea-treated DNA by immuno electron microscopy. J Cancer Res Clin Oncol 105:A23

    Google Scholar 

  • Nehls P, Rajewsky MF, Spiess E, Werner D (1984) Highly sensitive sites for guanine-O6-ethylation in rat brain DNA exposed to N-ethyl-N-nitrosourea in vivo. EMBO J 3: in press

    Google Scholar 

  • Plescia OJ (1968) Preparation and assay of nucleic acids as antigens. Meth Enzymol 12:893–899

    Article  CAS  Google Scholar 

  • Plescia OJ, Braun W, Palczuk NC (1964) Production of antibodies to denatured deoxyribonucleic acid (DNA). Proc Natl Acad Sci USA 52:279–285

    Article  PubMed  CAS  Google Scholar 

  • Poirier MC (1981) Antibodies to carcinogen-DNA adducts. J Natl Cancer Inst 67:515–519

    PubMed  CAS  Google Scholar 

  • Poirier MC, Yuspa SH, Weinstein IB, Blobstein S (1977) Detection of carcinogen-DNA adducts by radioimmunoassay. Nature 270:186–188

    Article  PubMed  CAS  Google Scholar 

  • Pokier MC, Dubin MA, Yuspa SH (1979) Formation and removal of specific acetylaminofluorene-DNA adducts in mouse and human cells measured by radioimmunoassay. Cancer Res 39:1377–1381

    Google Scholar 

  • Pokier MC, Santella R, Weinstein IB, Grunberger D, Yuspa SH (1980) Quantitation of benzo(a)py-rene-deoxyguanosine adducts by radioimmunoassay. Cancer Res 40:412–416

    Google Scholar 

  • Rajewsky MF (1980) Specificity of DNA damage in chemical carcinogenesis. In: Montesano R, Bartsch H, Tomatis L (eds) Molecular and cellular aspects of carcinogen screening tests. IARC Scientific Publications No 27. International Agency for Research on Cancer, Lyon, pp 41–54

    Google Scholar 

  • Rajewsky MF (1982) Pulse-carcinogenesis by ethylnitrosourea in the developing rat nervous system: molecular and cellular mechanisms. In: Nicolini C (ed) Chemical carcinogenesis. Plenum Press, New York, pp 363–379

    Google Scholar 

  • Rajewsky MF (1983) Structural modifications and repak of DNA in neurooncogenesis by N-ethyl-N-nitrosourea. Rec Res Cancer Res 84:63–76

    CAS  Google Scholar 

  • Rajewsky MF, Augenlicht LH, Biessmann H, Goth R, Hülser DF, Laerum OD, Lomakina LYa (1977) Nervous system-specific carcinogenesis by ethylnitrosourea in the rat: molecular and cellular mechanisms. In: Hiatt HH, Watson JD, Winsten JA (eds) Origins of human cancer. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 709–726

    Google Scholar 

  • Rajewsky MF, Müller R, Adamkiewicz J, Drosdziok W (1980) Immunological detection and quantification of DNA components structurally modified by alkylating carcinogens (ethylnitrosourea). In: Pullman B, Ts’o POP, Gelboin H (eds) Carcinogenesis: Fundamental mechanisms and envkon-mental effects. Reidel, Dordrecht Boston London, pp 207–218

    Chapter  Google Scholar 

  • Randerath K, Reddy MV, Gupta RC (1981) 32P-labeling test for DNA damage. Pròc Natl Acad Sci USA 78:6126–6129

    Article  PubMed  CAS  Google Scholar 

  • Saffhill R, Strickland PT, Boyle J (1982) Sensitive radioimmunoassays for O6-N-butyldeoxyguanosine, O2-N-butylthymidine and O6-N-butylthymidine. Carcinogenesis 3:547–552

    Article  PubMed  CAS  Google Scholar 

  • Sage E, Fuchs RPP, Leng M (1979) Reactivity of the antibodies to DNA modified by the carcinogen N-acetoxy-N-aminofluorene. Biochemistry 18:1328–1332

    Article  PubMed  CAS  Google Scholar 

  • Singer B (1979) N-nitroso alkylating agents: formation and persistence of alkyl derivatives in mammalian nucleic acids as contributing factors in carcinogenesis. J Natl Cancer Inst 62:1329–1339

    PubMed  CAS  Google Scholar 

  • Singer B, Kusmierek JT (1982) Chemical mutagenesis. Ann Rev Biochem 52:655–693

    Article  Google Scholar 

  • Spodheim-Maurizot M, Saint-Ruf G, Leng M (1979) Conformational changes induced in DNA by in vitro reaction with N-hydroxy-N-2-aminofluorene. Nucleic Acids Res 6:1683–1694

    Article  PubMed  CAS  Google Scholar 

  • Stollar BD, Borei Y (1976) Nucleoside specificity in the carrier IgG-dependent induction of tolerance. J Immunol 117:1308–1313

    PubMed  CAS  Google Scholar 

  • Town CD, Smith KC, Kaplan HS (1973) Repair of X-ray damage to bacterial DNA. Curr Top Rad Res Q 8:351–399

    CAS  Google Scholar 

  • Van der Laken CJ, Hagenaars AM, Hermsen G, Kriek E, Kuipers AJ, Nagel J, Scherer E, Welling M (1982) Measurement of O6-ethyldeoxyguanosine and N-(deoxyguanosine-8-yl)-N-acetyl-2-amino-fluorene in DNA by high-sensitive enzyme immunoassays. Carcinogenesis 3:569–572

    Article  Google Scholar 

  • Wang S-Y (1976) Photochemistry and photobiology of nucleic acids. Academic Press, New York

    Google Scholar 

  • Waring MJ (1981) DNA modification and cancer. Ann Rev Biochem 50:159–192

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1984 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Adamkiewicz, J., Ahrens, O., Rajewsky, M.F. (1984). High-Affinity Monoclonal Antibodies Specific for Deoxynucleosides Structurally Modified by Alkylating Agents: Applications for Immunoanalysis. In: Eisert, W.G., Mendelsohn, M.L. (eds) Biological Dosimetry. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69334-2_30

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-69334-2_30

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-12790-1

  • Online ISBN: 978-3-642-69334-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics