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  • Title: Tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate enhances sister chromatid exchanges and numerical and structural chromosome aberrations in primary mouse epidermal cell cultures.
    Author: Dzarlieva RT, Fusenig NE.
    Journal: Cancer Lett; 1982; 16(1):7-17. PubMed ID: 7116341.
    Abstract:
    The tumor 12-O-tetradecanoyl-phorbol-13-acetate (TPA) moderately stimulated sister chromatid exchanges in primary epidermal cultures (PEC) from C3H mice, and strongly enhanced structural chromosome aberrations. In G-banded metaphases for TPA (10-(8) and 10-(6) M for 54 h) treated PEC aneuploidy (hypo- and hyperdiploidy) increased and structural aberrations were enhanced 8- to 10-fold. Breaks, fragments and metacentric chromosomes had raised 7- to 11-fold. Chromatid interchanges (tri- and quadri-radials) and centromeric splitting, virtually absent in controls, appeared in 4--8% of metaphases. The non-promoting 4-O-methyl-TPA did not induce chromosomal alterations. These substantial effects on the genetic material of target cells represent a new aspect of the mechanism of action of tumor-promoting phorbol esters.
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