Tumor promoter 12- O-tetradecanoyl-phorbol-13-acetate enhances sister chromatid exchanges and numerical and structural chromosome aberrations in primary mouse epidermal cell cultures

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 from 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 quadriradials) 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 tumorpromoting phorbol esters.