Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action
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.
- Publication:
-
Nature
- Pub Date:
- September 1981
- DOI:
- 10.1038/293144a0
- Bibcode:
- 1981Natur.293..144E