Die Onkologie pp 193-240 | Cite as

Mehrstufenprozess der Kanzerogenese und chemische Kanzerogenese

  • R. Schulte-Hermann
  • W. Parzefall

Zusammenfassung

Die heutigen Vorstellungen zum Mechanismus der Krebsentstehung wurden seit der zweiten Hälfte des 19. Jahrhunderts konzipiert.Virchow (1863) postulierte, dass Krebs durch chronische Gewebereizung ausgelöst wird. Boveri (1914) und Bauer (1928) erkannten die Bedeutung chromosomaler Veränderungen und somatischer Mutationen für die Kanzerogenese. Einen entscheidenden Fortschritt für die Erforschung von Ursachen und Mechanismen der Krebsentstehung ermöglichte die Einführung von Tierversuchen. 1915 bewiesen Yamagiwa und Ichikawa im Experiment am Kaninchen, dass Teer Hautkrebs erzeugen kann und bestätigten damit ältere Vermutungen, die auf Beobachtungen am Menschen basierten. Als spezifische kanzerogene Wirkstoffe des Teers wurden die polyzyklischen aromatischen Kohlenwasserstoffe (PAK) identifiziert (Kennaway 1955). In Modelluntersuchungen an der Mäusehaut wurde die Rolle von PAK und von Gewebereizungen für die Tumorentstehung studiert. Eine einmalige, niedrige Dosis von PAK oder wiederholte Entzündungen durch Aufpinseln von Crotonöll erzeugten für sich alleine keine Hauttumoren, gemeinsam jedoch waren sie stark wirksam (Berenblum 1941). Als entscheidend erwies sich die Reihenfolge der Behandlung: Tumoren traten nur auf, wenn erst PAK, dann Crotonöl auf die Haut aufgetragen wurde, die umgekehrte Sequenz war unwirksam. Daraus wurde abgeleitet, dass die Entstehung von Krebs eine Abfolge unterschiedlicher biologischer Vorgänge erfordert. Der erste, im Modell durch PAK induzierte Vorgang wurde Initiation genannt, der zweite, die Tumorentstehung fördernde Prozess Promotion. Zunächst entstanden gutartige Tumoren (Papillome), die sich nach Behandlungsende in der Mehrzahl zurückbildeten. In einem anschließenden Stadium, das als Progression bezeichnet wird, entwickelten sich Karzinome. Spätere Tierexperimente zeigten, dass die Kanzerogenese auch in anderen Organen über die Stufen Initiation, Promotion und Progression erfolgt.

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© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • R. Schulte-Hermann
  • W. Parzefall

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