Deacylation of 12-O-[3H]tetradecanoylphorbol-13-acetate and [3H]phorbol-12,13-didecanoate in hamster skin and hamster cells in culture.

The deacylation of tritium-labeled 12-O-tetradecanoylphorbol-13-acetate ([3H]TPA) and tritium-labeled phorbol-12,13-didecanoate ([3H]PDD) by hamster cells in culture and hamster skin in vivo was studied. Cell cultures of Syrian hamster embryo fibroblasts and preneoplastic or neoplastic derivatives of these cells deacylated [3H]TPA rapidly, and the major product ob served cochromatographed on silica gel thin-layer chromatographs with phorbol-13-acetate. [3H]PDD was more stable un der the same conditions although some radioactivity corre sponding to phorbol-12-decanoate was observed. Cultures of dermal fibroblasts and epidermal cells from 1-day-old hamster deacylated [3H]TPA to phorbol-13-acetate but at a slower rate than observed with Syrian hamster embryo cells. [3H]PDD was also more stable than was [3H]TPA in these cultures, but the difference between the stability of these two phorbol ester derivatives was less pronounced in the presence of skin cells than in the presence of embryo cells. In contrast to the degra dation of [3H]TPA and [3H]PDD observed by cells in culture, no deacylation on the phorbol diesters in intact hamster skin was detected. The compounds were cleared from hamster skin at a rate comparable to that observed in mouse skin. The radio activity extracted from hamster skin for up to 48 hr after treatment appeared to be unchanged TPA or PDD. Pretreat ment of hamster skin with 50 u.g of TPA twice per week for 4 weeks did not alter the rate of clearance or the deacylation of [3H]TPA. These results indicate that hamster cells in culture can deacylate phorbol diesters, but in intact hamster skin, the rate of deacylation of TPA or PDD is not measurably different from that of mouse skin. These findings do not support the concept that the lack of TPA-induced tumor promotion in hamsters is due to metabolic inactivation of the promoter.