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DNA Adducts and Carcinogenesis

  • Frederick A. Beland
  • Miriam C. Poirier

Abstract

A central tenet of cancer research is that tumors arise from cells that have undergone a permanent heritable change in their genetic material. This hypothesis originated from the observation that tumor cells have lost normal growth-control mechanisms and transmit this characteristic to their progeny. It is supported by the findings that most chemically induced tumors are monoclonal in origin1 and that consistent cytogenetic changes are present in certain tumors.2 Although a number of mechanisms can be envisaged to explain the origin of these heritable genetic changes (e.g., see Chapters 4 and 5), clearly the dominant theme in present-day carcinogenesis is that in most instances they arise from the interaction between chemical carcinogens and DNA. This belief is supported by a number of observations, including the facts that (1) most carcinogens are also mutagens; (2) the mutagenic and carcinogenic properties of many compounds depend on their in vivo conversion into electrophilic derivatives that react with nucleophilic sites within DNA to form covalent adducts; (3) the extent of DNA adduct formation can often be correlated with mutagenic and carcinogenic responses; and (4) the activation of specific DNA sequences, termed protooncogenes, can be accomplished through the interaction of chemical carcinogens with DNA (see Chapter 14).

Keywords

Aromatic Amine Chemical Carcinogen Thymic Lymphoma Diol Epoxide Aromatic Amide 
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.

Abbreviations used in this chapter

2-AAF

2-acetylaminofluorene

AcCoA

acetyl coenzyme A

AFB1

aflatoxin B1

AFB1-N7-Gua

trans-8,9-dihydro-8-(guan-7-yl)-9-aflatoxin B1

AFB1-N7-dG-DNA

DNA modified with trans-8,9-dihydro-8-(deoxyguanosin-7-yl)-9-aflatoxin B1

AFB1-N7-Pyrmaj

8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-y1 formamido)-9-hydroxyaflatoxin B1

AFB1-N7-Pyrmin

8,9-dihydro-8-(2-amino-6-formamido-4-oxo-3,4-dihydropyrimid-5-y1 amino)-9-hydroxyaflatoxin B1

AFBI-diol

8,9-dihydro-8,9-dihydroxyaflatoxin B1

BaP

benzo[a]pyrene

dG-C8-AF

N-(deoxyguanosin-8-y1)-2-aminofluorene

dG-C8-AAF

N-(deoxyguanosin-8-yl)-2-acetylaminofluorene

dG-N2-AAF

3-(deoxyguanosin-N 2-y1)-2-acetylaminofluorene

DMN

N-nitrosodimethylamine

ELISA

enzyme-linked immunosorbent assay

HPLC

high-pressure liquid chromatography

MMS

methylmethanesulfonate

MNU

N-methyl-N-nitrosourea

NNK

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

PAH

polycyclic aromatic hydrocarbons

PAPS

3’-phosphoadenosine 5’-phosphosulfate

RIA

radioimmunoassay

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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Frederick A. Beland
    • 1
  • Miriam C. Poirier
    • 2
  1. 1.National Center for Toxicological ResearchJeffersonUSA
  2. 2.National Cancer InstituteNational Institutes of HealthBethesdaUSA

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