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  • 1
    ISSN: 1432-1335
    Keywords: Tumorpromoter ; Phorbol ; Diterpene ; Leukemogenesis cocarcinogens ; Tumorpromotor ; Cocarcinogene ; Phorbol ; Diterpen ; Leukämogenese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Phorbol und sechs strukturverwandte Substanzen, die die polyfunktionellen Diterpene des Tiglian-, Ingenan- und Lathyrantyps repräsentieren, wurden an SWR-Mäusen auf systemische promovierende und leukämogene Wirkung geprüft. Zur systemischen Initiation wurde kurz nach Geburt 15 μg Dimethylnitrosamin (DMN) s.c. injiziert. Die Diterpene wurden i.p. entweder mit oder ohne vorhergehende Initiation mit DMN gegeben. Systemische Promotion für Leber zeigten alle geprüften Diterpene mit der Entstehung von Adenomen. Einige der Diterpene erwiesen sich wirksamer als Phorbol. Die relativ hohe Dosis von DMN, die als Initiator verwendet wurde, machte eine Auswertung bezüglich promovierender Wirkung auf die Lunge unmöglich. Die leukämogene Wirkung von Phorbol bei SWR Mäusen wurde für drei verschiedene Dosen bestätigt. Die übrigen Diterpene zeigten mit der jeweils geprüften Dosis keine signifikante leukämogene Wirkung. Die leukämogene Wirkung des Phorbols wurde durch vorausgehende DMN-Injektion vollständig verhindert. Die fehlende Korrelation zwischen promovierender Wirkung an Haut, systemischer promovierender Wirkung an Leber und leukämogener Wirkung der getesteten Diterpene wird diskutiert.
    Notes: Summary Phorbol and six structurally related compounds representing the polyfunctional diterpenes of the tigliane, ingenane, and lathyrane types were tested for systemic promoting and leukemogenic activity in SWR mice. For systemic initiation soon after birth, 15 μg dimethylnitrosamine (DMN) was injected s.c. The diterpenes were administered i.p. either with or without prior systemic initiation with DMN. Systemic promotion was expressed for liver by induction of adenomas with all the diterpenes tested, some of them being more potent than phorbol. The relatively high dose of DMN used as initiator prevented an evaluation of promoting action in relation to lung carcinogenesis. The leukemogenic effect of phorbol in SWR mice was confirmed at three different dose levels. The other diterpenes tested had no significant leukemogenic activity. The leukemogenic action of phorbol was totally inhibited by prior DMN injection. The lack of correlation between promoting action in skin, systemic promoting action in liver and leukemogenic action, among the diterpenes tested, is discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Diterpene ; Tumorpromoter ; Plasminogen-Aktivator ; Blutplättchen-Aggregation ; Diterpene ; Tumor promoter ; Plasminogen activator ; Platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Phorbol and eight of its derivatives were investigated for their ability to stimulate the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts and to aggregate human blood platelets and have been assayed for tumor, promoting and skin, irritant activities. Over a range of concentrations, elevation in the levels of plasminogen activator activity induced by phorbol derivatives correlates well with their promoting and irritant properties. In the platelet aggregation assay however, the parallelism between the activities measured in different biological assays was less complete. While strong promoters, such as TPA, are potent aggregating agents, and weak promoters, such as PDA, are poor or ineffective inducers of aggregation, two derivatives, PDD and PDB, deviate from this general result. Platelets must be exposed to PDD in relatively high concentrations before they will aggregate, and PDB was found to be the most potent aggregating agent of all the derivatives tested.
    Notes: Zusammenfassung Phorbol und acht seiner Derivate wurden auf ihre Fähigkeit untersucht, die Synthese von Plasminogen-Aktivator in Zellkulturen von Hühnerembryo-Fibroblasten zu stimulieren und die Aggregation von Blutplättchen zu induzieren und auf ihre tumorpromovierende und hautirritierende Wirkung getestet. Die Erhöhung der Plasminogen-Aktivator Aktivität durch Phorbolderivate korreliert gut mit ihren irritierenden und promovierenden Eigenschaften. Im Test auf Blutplättchen-Aggregation ist die Korrelation nicht eindeutig: Sie gilt für starke Promotoren (wie TPA), die auch hochwirksame Induktoren der Aggregation sind, sowie für schwache Promotoren (wie PDA), die nur gering oder nicht induzieren; Ausnahmen sind PDD und PDB: PDD, ein starker Promoter, ist nur schwach wirksam, PDB, ein schwacher Promotor, ist dagegen das am stärksten aggregationsstimulierende Derivat.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 103 (1982), S. 17-29 
    ISSN: 1432-1335
    Keywords: Diterpene ; Tumor promoter ; Differentiation ; Leukemia cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 12-O-Tetradecanoylphorbol-13-acetate (TPA), the prototype polyfunctional diterpene ester tumor promoter of two-step carcinogenesis in mouse skin, induced differentiation of human promyelocytic leukemia cells (HL-60) in culture. Differentiation of HL-60 cells was characterized by increased phagocytosis, increased lysozyme activity (EC 3.2.1.17) in the growth medium, and changes in morphology to those characteristics of more mature cells resembling macrophages. Many of the cells treated with TPA became aggregated, attaching firmly to culture flasks. The average intracellular myeloperoxidase activity (EC 1.11.1.7) per cell decreased during induction of differentiation by TPA. It was also found that TPA enhanced, rather than inhibited, differentiation of HL-60 cells induced by DMSO. In addition to TPA, several polyfunctional diterpene esters of the tigliane, ingenane, and daphnane type have been tested for their ability to induce morphological and functional changes of HL-60 cells. The activities of the compounds to induce these changes correlated well with their activities as tumor promoters in two-step carcinogenesis in mouse skin. In particular, half the concentrations required for induction of adhesion of the cells to flasks were roughly correlated to the potency of these compounds as tumor promoters. Among the compounds tested, phorbol-12,13-didecanoate (PDD), ingenol-3-hexadecanoate, Pimelea factor P1 and Pimelea factor P2 were as active as TPA, while 4-O-methyl-TPA and 4α-PDD were much less active. Phorbol and ingenol were totally inactive up to a concentrations 10,000-fold higher than that of TPA.
    Type of Medium: Electronic Resource
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