Skip to main content
SpringerLink
Log in

Genotoxic and Chronic Toxic Effects in the Carcinogenicity of Aromatic Amines

  • Conference paper
Risk and Progression Factors in Carcinogenesis

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 143))

Abstract

Many polycyclic aromatic amines are mutagenic, and their genotoxic properties are held responsible for their biological effects. The genotoxic effects are explained by the formation of metabolites that react with macromolecules by forming adducts (Kriek 1969; Franz et al. 1986). DNA adducts may cause mutations which are responsible for tumorigenic effects. Results from comparative studies, however, indicate that tissue-specific and species-specific tumor formation caused by arylamines cannot be explained readily by the extent of DNA modifications. Long-term feeding of 2-acetylaminofluorene (AAF) typically produces liver tumors; 2-acetylaminophenanthrene (AAP), mammary tumors; andtrans-4-acetylaminostilbene (AAS), Zymbal’s gland tumors in rats (Neumann et al. 1970). All three arylamines are genotoxic. They generate comparable DNA adduct levels in rat liver, and in liver more extensively than in any other tissue (Neumann 1983; Ruthsatz and Neumann 1988; Gupta et al. 1989). But only AAF is a complete carcinogen in rat liver. AAS and AAP are able to produce liver tumors in rats only, if initiation is followed by some promotion treatment (Hammerl 1989). Therefore, DNA binding may reflect the formation of some critical lesions related to tumor initiation but is not sufficient to explain carcinogenic effects. This raises two questions: (1) Do differences in genotoxic initiating effects contribute to tissue specificity? and (2) What are the additional promoting properties of AAF that distinguish it from the incomplete liver carcinogens?

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

Access this chapter

Log in via an institution
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 EPUB and 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

  • Ambs S (1992) Die Bedeutung von oxidativem Stress in Rattenlebermitochondrien für die Erzeugung chronisch toxischer Effekte durch karzinogene aromatische Amine. Dissertation, Naturwissenschaftliche Fakultät, University of Würzburg

    Google Scholar 

  • Beckmann RP, Mizzen LA, Welsh WJ (1990) Interaction of hsp70 with newly synthesized proteins: implications for folding and assembly. Science 248: 850–854

    Article  PubMed  CAS  Google Scholar 

  • Bitsch A, Röschlau H, Deubelbeiss C, Neumann H-G (1993) The structure and function of the H-ras-protooncogene are not altered in rat liver tumors initiated by 2-acet- ylaminofluorene, 2-acetylaminophenanthrene and trans-4-acetylaminostilbene. Toxicol Lett 67: 173–186

    Article  PubMed  CAS  Google Scholar 

  • Calder IC, Williams PJ (1974) The synthesis and reactions of some carcinogenic N-(2-phenanthryl)hydroxylamine derivatives. Aust J Chem 27: 1791–1795

    Article  CAS  Google Scholar 

  • Donati YR, Slosman DO, Polla BS (1990) Oxidative injury and the heat shock response. Biochem Pharmacol 40: 2571–2577

    Article  PubMed  CAS  Google Scholar 

  • Floyd RA, Soong LM, Walker RN, Stuart M (1976) Lipid hydroperoxide activation of N-hydroxy-N-acetylaminofluorene via a free radical route. Cancer Res 36: 2761–2767

    PubMed  CAS  Google Scholar 

  • Franz R, Schulten HR, Neumann H-G (1986) Identification of nucleic acid adducts from trans-4-acetylaminostilbene. Chem Biol Interact 59: 281–293

    Article  PubMed  CAS  Google Scholar 

  • Gupta RC, Earley K, Fullerton NF, Beland FA (1989) Formation and removal of DNA adducts in target and nontarget tissues of rats administered multiple doses of 2-acetophenanthrene. Carcinogenesis 10: 2025–2033

    Article  PubMed  CAS  Google Scholar 

  • Hammerl R (1989) Zur synergistischen Wirkung aromatischer Amine bei der Initiierung von Tumoren in der Rattenleber. Dissertation, Tiermedizinische Fakultät, University of Munich

    Google Scholar 

  • Hammerl R, Kirchner T, Neumann H-G (1994) Synergistic effects of trans-4-acet- ylaminostilbene and 2-acetylaminofluorene at the level of tumor initiation. Chem Biol Interact 93: 11–28

    Article  PubMed  CAS  Google Scholar 

  • Klöhn PC, Massalha H, Neumann H-G (1995) A metabolite of carcinogenic 2-acet-ylaminofluorene, 2-nitrosofluorene, induces redox cycling in mitochondria. Biochim Biophys Acta 1229: 363–372

    Article  PubMed  Google Scholar 

  • Kriek E (1969) On the mechanism of action of carcinogenic aromatic amines. I. Binding of 2-acetylaminofluorene and N-hydroxy-2-acetylaminofluorene to rat liver nucleic acids in vivo. Chem Biol Interact 1: 3–17

    Article  PubMed  CAS  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685

    Article  PubMed  CAS  Google Scholar 

  • Lindquist S, Craig EA (1988) The heat shock proteins. Annu Rev Genet 22: 631–677

    Article  PubMed  CAS  Google Scholar 

  • Lotlikar PD, Miller EC, Miller JA, Margreth A (1965) The enzymatic reduction of the N-hydroxy derivatives of 2-acetylaminofluorene and related carcinogens by tissue preparations. Cancer Res 25: 1743–1752

    PubMed  CAS  Google Scholar 

  • Massalha H, Klöhn P-C, Neumann H-G (1994) 2-Nitrosofluorene effects on rat liver mitochondria: superoxide production, lipid peroxidation and a dual effect on respiration. Naunyn Schmiedebergs Arch Pharmacol [Suppl] 349: R128

    Google Scholar 

  • McGregor D (1988) The activities of 2-acetylaminofluorene, 4-acetylaminofluorene, benzo(a)pyrene and pyrene in in vitro assays for genetic toxicity. In: Ashby J, de Serres FJ, Shelby MD, Margolin BH, Ishidate M Jr, Becking GC (eds) Report of the international programme on chemical safety’s collaborative study on in vivo assays, vol. 2. Cambridge University Press, Cambridge, pp 345–350

    Google Scholar 

  • Metzler M, Neumann H-G (1971) Zur Bedeutung chemisch-biologischer Wechselwirkungen für die toxische und krebserzeugende Wirkung aromatischer Amine. III Synthese und Analytik einiger Stoffwechselprodukte von trans-4-Dimethylamino- stilben, cis-4-Dimethylaminostilben und 4-Dimethylaminobibenzyl. Tetrahedron 27: 2225–2246

    Article  CAS  Google Scholar 

  • Mulligan RC, Berg P (1981) Selection for animal cells that express theEscherichia coli gene coding for xanthine guanine phosphoribosyl transferase. Proc Natl Acad Sci USA 78: 2072–2076

    Article  PubMed  CAS  Google Scholar 

  • Neumann H-G (1983) Role of extent and persistence of DNA modifications in chemical carcinogenesis by aromatic amines. In: Rentchnick P, Herfarth C, Senn HJ (eds) Recent results in cancer research, vol 84. Springer, Berlin Heidelberg New York, pp 77–89

    Google Scholar 

  • Neumann H-G (1986) The role of DNA damage in chemical carcinogenesis of aromatic amines. J Cancer Res Clin Oncol 112: 100–106

    Article  PubMed  CAS  Google Scholar 

  • Neumann H-G, Metzler M, Brachmann I, Thomas C (1970) Zur Bedeutung chemischbiologischer Wechselwirkungen für die toxische und krebserzeugende Wirkung aromatischer Amine. I. Krebserzeugende Wirksamkeit einiger 4-Aminostilben und 4- Aminobibenzyl-Verbindungen. Z Krebsforsch 74: 200

    Article  PubMed  CAS  Google Scholar 

  • Neumann H-G, Ambs S, Hilleshein H (1992) The biochemical basis of hepatotoxicity. In: Dekant W, Neumann H-G (eds) Tissue specific toxicity, biochemical mechanisms. Academic Press, London, pp 139–162

    Google Scholar 

  • Neumann H-G, Ambs S, Bitsch A (1994) The role of nongentoxic mechanisms in arylamine carcinogenesis. Environ Health Perspect 102 [Suppl 6]: 173–176

    Article  PubMed  CAS  Google Scholar 

  • O’ Farrel PH (1975) High resolution two-dimensional electrophoresis of proteins. J BiolChem 250: 4007–4021

    Google Scholar 

  • Peraino C, Staffeldt EF, Ludeman VA (1981) Early appearance of histochemically altered hepatocyte foci and liver tumors in female rats treated with carcinogens one day after birth. Carcinogenesis 2: 463–4165

    Article  PubMed  CAS  Google Scholar 

  • Rothman JR (1990) Polypeptide chain binding porteins: catalysts of protein folding and related processes in cells. Cell 59: 591–601

    Article  Google Scholar 

  • Ruthsatz M, Neumann H-G (1988) Synergistic effects on the initiation of rat liver tumors by trans-4-acetylaminostilbene and 2-acetylaminofluorene, studied at the level of DNA adduct formation. Carcinogenesis 9: 265–269

    Article  PubMed  CAS  Google Scholar 

  • Sato K, Kithara A, Satoh H (1984) The placental form of glutathione-S-transferase as a marker protein for neoplasia in rat chemical hepatocarcinogenesis. GANN 75: 199–202

    PubMed  CAS  Google Scholar 

  • Stankowski LF, Tindali KR, Hsie AW (1986) Quantitative and molecular analyses of ethylmethanesulfonate- and ICR191 induced mutations in AS52 cells. Mutat Res 160: 133–147

    Article  PubMed  CAS  Google Scholar 

  • Von Jagow G, Klingenberg M (1972) Close correlation between antimycin titer and cytochrome bT content in mitochondria of chloramphenicol-treatedNeurospora crassa. FEBS Lett 24: 278–282

    Article  Google Scholar 

  • Neumann H-G (1986) The role of DNA damage in chemical carcinogenesis of aromatic amines. J Cancer Res Clin Oncol 112: 100–106

    Article  PubMed  CAS  Google Scholar 

  • Welch WJ (1992) Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 72: 1063–1081

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany

    A. Bitsch, J. Fecher, M. Jost, P.-C. Klöhn & H.-G. Neumann

Authors
  1. A. Bitsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Fecher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Jost
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P.-C. Klöhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H.-G. Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pathologisches Institut, der Universität Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany

    H. K. Müller-Hermelink

  2. Institut für Pharmakologie und Toxikologie, der Universität Würzburg, Versbacher Straße 9, 97078, Würzburg, Germany

    H.-G. Neumann  & W. Dekant  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

Bitsch, A., Fecher, J., Jost, M., Klöhn, PC., Neumann, HG. (1997). Genotoxic and Chronic Toxic Effects in the Carcinogenicity of Aromatic Amines. In: Müller-Hermelink, H.K., Neumann, HG., Dekant, W. (eds) Risk and Progression Factors in Carcinogenesis. Recent Results in Cancer Research, vol 143. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60393-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60393-8_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64385-9

  • Online ISBN: 978-3-642-60393-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation