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Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action

Nature volume 293, pages 144–146 (1981)Cite this article

Abstract

The mouse skin tumour promoter phorbol-12-myristate-13-acetate (PMA) does not form covalent adducts with cellular DNA and its mutagenic potency in several systems is low or absent1–6. There have been conflicting reports of the capacity of PMA to produce sister chromatid exchanges (SCEs)3,6–8. As PMA induces the formation of superoxide radicals in polymorphonuclear leukocytes and mitogen-stimulated lymphocytes9–11, we suggested that it might produce DNA damage via indirect action by the formation of intermediate active oxygen species12,13. As is typical for other DNA-damaging agents which mainly act indirectly, for example, ionizing radiation, PMA would be expected to have low mutagenicity but high clastogenic (chromosome-breaking) activity14. In agreement with this, we report here that PMA, but not its weakly or non-promoting derivatives, induced chromosomal aberrations with high efficiency in phytohaemagglutinin (PHA)-stimulated human lymphocytes, but was only a weak producer of SCE. This activity was suppressed by superoxide dismutase, which catalyses the breakdown of superoxide radicals.

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Authors and Affiliations

  1. Laboratory of Experimental Cytogenetics, Institut Biomédical des Cordeliers, Université Pierre et Marie Curie, 15, Rue de l'Ecole de Médecine, Paris, VI, France

    Ingrid Emerit

  2. Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, CH-1066, Epalinges s./Lausanne, Switzerland

    Peter A. Cerutti

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  1. Ingrid Emerit
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  2. Peter A. Cerutti
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Emerit, I., Cerutti, P. Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action. Nature 293, 144–146 (1981). https://doi.org/10.1038/293144a0

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