Tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate enhances sister chromatid exchanges and numerical and structural chromosome aberrations in primary mouse epidermal cell cultures.
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.
D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000648:ultrastructure; D003434:Crossing Over, Genetic / Q000187:drug effects*; D008214:Lymphocytes; D051379:Mice; D008809:Mice, Inbred C3H; D010704:Phorbols / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012867:Skin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate