DNA Adducts and Their Biological Relevance

Doerjer, Gerhard; Bedell, Mary A.; Oesch, Franz

doi:10.1007/978-3-642-69530-8_2

Cited by 11 publications

(5 citation statements)

References 44 publications

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“…Although total adduct formation in DNA in some cases could not be correlated with tumor formation (17), it may well be that a specific type of lesion among the various adducts that are induced is directly related to the development of neoplasia or the occurrence of heritable disorder (52). At the same time, additional research is necessary to provide a basis for interpretation of positive.…”

Section: Discussionmentioning

confidence: 99%

Use of Monoclonal and Polyclonal Antibodies against DNA Adducts for the Detection of DNA Lesions in Isolated DNA and in Single Cells

Baan¹,

Zaalberg²,

Fichtinger-Schepman³

et al. 1985

Environmental Health Perspectives

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JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives. Interaction of genotoxic chemicals with their intracellular target, i.e., DNA, may result in the formation of covalent adducts. Various methods have been developed to estimate exposure to genotoxic chemicals by means of molecular dosimetry of DNA adducts. Such experiments have generally been carried out with radiolabeled genotoxicants administered in vitro to cultured cells or in vivo to laboratory animals. Biomonitoring of human exposure to genotoxic chemicals requires methods to detect very small quantities of nonradioactive DNA adducts in limited amounts of sample.Attention has been devoted to the development of immunochemical techniques in which specific DNA adducts can be detected with antibodies. The level of sensitivity achieved in these experiments renders these methods applicable for human biomonitoring. When suitable antibodies are available, the immunochemical approach enables one to analyze various types of adducts separately, and to discriminate between irrelevant (e.g., quickly repairable) and relevant lesions (key lesions) with respect to biological end points such as mutation induction and cancer.Polyclonal and monoclonal antibodies were used for the detection of DNA adducts in animal and human tissue. Adducts were measured in DNA from various organs of rats treated with the liver carcinogen 2-AAF. Human exposure to genotoxic agents was studied by the measurement of DNA adducts in blood cells from patients treated with the genotoxic cytostatic cisplatin. Also, the development is described of a system to detect and quantitate DNA adducts at the single-cell level by means of immunofluorescence microscopy, which allows the analysis of small samples of human tissue with preservation of cell morphology.

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Section: Discussionmentioning

confidence: 99%

Use of Monoclonal and Polyclonal Antibodies against DNA Adducts for the Detection of DNA Lesions in Isolated DNA and in Single Cells

Baan¹,

Zaalberg²,

Fichtinger-Schepman³

et al. 1985

Environmental Health Perspectives

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show abstract

“…Such experiments may reveal which of the various adducts is responsible for the induction of the genetic effects observed (i.e., the key lesion). Although total adduct formation in DNA in some cases could not be correlated with tumor formation (17), it may well be that a specific type of lesion among the various adducts that are induced is directly related to the development of neoplasia or the occurrence of heritable disorder (52). Total adduct formation, e.g., measured in various organs after treatment of an animal with radiolabeled genotoxicants, does not necessarily reflect the relative abundance of these key lesions, because various types of damage may follow different, organspecific kinetics of formation and repair.…”

Section: Discussionmentioning

confidence: 99%

Use of monoclonal and polyclonal antibodies against DNA adducts for the detection of DNA lesions in isolated DNA and in single cells.

Baan¹,

Zaalberg²,

Fichtinger-Schepman³

et al. 1985

Environ Health Perspect

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Interaction of genotoxic chemicals with their intracellular target, i.e., DNA, may result in the formation of covalent adducts. Various methods have been developed to estimate exposure to genotoxic chemicals by means of molecular dosimetry of DNA adducts. Such experiments have generally been carried out with radiolabeled genotoxicants administered in vitro to cultured cells or in vivo to laboratory animals. Biomonitoring of human exposure to genotoxic chemicals requires methods to detect very small quantities of nonradioactive DNA adducts in limited amounts of sample. Attention has been devoted to the development of immunochemical techniques in which specific DNA adducts can be detected with antibodies. The level of sensitivity achieved in these experiments renders these methods applicable for human biomonitoring. When suitable antibodies are available, the immunochemical approach enables one to analyze various types of adducts separately, and to discriminate between irrelevant (e.g., quickly repairable) and relevant lesions (key lesions) with respect to biological end points such as mutation induction and cancer. Polyclonal and monoclonal antibodies were used for the detection of DNA adducts in animal and human tissue. Adducts were measured in DNA from various organs of rats treated with the liver carcinogen 2-AAF. Human exposure to genotoxic agents was studied by the measurement of DNA adducts in blood cells from patients treated with the genotoxic cytostatic cisplatin. Also, the development is described of a system to detect and quantitate DNA adducts at the single-cell level by means of immunofluorescence microscopy, which allows the analysis of small samples of human tissue with preservation of cell morphology.ImagesFIGURE 1.

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“…Die Bestimmung von Hämoglobinkonjugaten liefert daher nur ein generelles, kein organspezifisches DosisMonitoring zellulärer Aminoaromaten-Belastungen [50]. Beim Menschen konnte eine bei einigen Tierspezies für einzelne Aminoaromaten nachgewiesene Parallelität zwischen Hämoglobin-und DNA-Bindung [3] bisher nicht bestätigt werden [50,54,55]. Im Hinblick auf die individuellen Repair-Mechanismen und die für die eigentliche Tumorentstehung wesentlichen Stoffwechselvorgänge, wie z.…”

Section: Metabolismus Und Wirkungsweiseunclassified

“…Speziesunterschiede zeigen [20,24,25], entscheiden offenbar die inter-und intraindividuellen Polymorphismen aller übrigen am Aminoaromaten-Stoffwechsel beteiligten Enzyme, insbesondere die N-Acetyl-sowie Arylhydroxamsäure-N,O-acyltransferasen [2,20,24,25,35,47], letztendlich darüber, ob es zur �Giftung� oder �Ent-giftung� der Aminoaromaten kommt. Hierin könnte eine von vielen Erklärungsmög-lichkeiten der interindividuell unterschiedlichen carcinogenen Wirkungen einzelner Aminoaromaten liegen [35,54,58,59] [60]. Die bisherige arbeitsmedizinische Bewertung innerer Aminoaromatenbelastungen und -beanspruchungen erfährt zur Zeit eine wesentliche Umorientierung.…”

Section: Metabolismus Und Wirkungsweiseunclassified

Aromatische Amine (Anilin, o‐, m‐, p‐Toluidin, 4‐Chlor‐o‐toluidin, 2,4‐ und 2,6‐Toluylendiamin, 4‐Aminodiphenyl, 4,4′‐Diaminodiphenylmethan) [Biomonitoring Methods in German language, 1994]

Lewalter¹,

Biedermann²

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Analytische Methoden zur Prüfung gesundheitsschädlicher Arbeitsstoffe: Analysen in biologischem Material , 11. Lieferung, Ausgabe 1994 Der Artikel enthält folgende Kapitel: Grundlage des Verfahrens Geräte, Chemikalien und Lösungen Geräte Chemikalien Lösungen Vergleichsstandards Probenahme und Probenaufbereitung Probenahme Probenvorbehandlung Probenaufbereitung Derivatisierung Gaschromatographische Arbeitsbedingungen Analytische Bestimmung Kalibrierung Berechnung des Analysenergebnisses Beurteilung des Verfahrens Präzision Richtigkeit Nachweisgrenze Störeinflüsse Diskussion der Methode

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DNA Adducts and Their Biological Relevance

Cited by 11 publications

References 44 publications

Use of Monoclonal and Polyclonal Antibodies against DNA Adducts for the Detection of DNA Lesions in Isolated DNA and in Single Cells

Use of Monoclonal and Polyclonal Antibodies against DNA Adducts for the Detection of DNA Lesions in Isolated DNA and in Single Cells

Use of monoclonal and polyclonal antibodies against DNA adducts for the detection of DNA lesions in isolated DNA and in single cells.

Aromatische Amine (Anilin, o‐, m‐, p‐Toluidin, 4‐Chlor‐o‐toluidin, 2,4‐ und 2,6‐Toluylendiamin, 4‐Aminodiphenyl, 4,4′‐Diaminodiphenylmethan) [Biomonitoring Methods in German language, 1994]

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