Influence of short-term topical exposure to phorbol ester tumor promoters on subcutaneously induced skin tumorigenesis in S/RV Cri mice

Abstract

The effects of short-term exposure to phorbol ester tumor promoters on epithelial and mesenchymal skin tumor induction, studied histologically in female S/RVCri mice, rendered precancerous by a subcutaneous (sc) injection of 3-methylcholanthrene (MCA). At 6 weeks after MCA injection, mice in Groups I to VI received topical twice weekly applications of 0.1 ml acetone, 1.8 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol didecanoate (PDD), phorbol dibenzoate (PDB), phorbol diacetate (PDA) or 6.1 nmol mezerein (MEZ) in 0.1 ml acetone, respectively, for four weeks. Animals were sacrificed after the development of palpable tumors. Data from various phorbol ester treatment groups were compared with the acetone control. Of the promoters tested, TPA treatment increased the percentage of tumor bearers and the number of combinations and expression of diverse neoplasms in the mixed growths. TPA-related phorbol esters such as PDD, PDB or MEZ did not alter the percentage of tumor bearers although the histological distribution into pure epithelial or mesenchymal and mixed tumor bearers differed significantly from the control treated with the solvent alone. However, PDA significantly inhibited MCA-induced skin tumorigenesis and increased the average time of tumor induction. All the promoters, except TPA, decreased the percentage of mixed tumor bearers, the development of hibernoma and fibrosarcoma, while allowing a selective expression of rhabdomyosarcoma.