Long-term treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) of dorsal skin of 7,12-dimethylbenz(a)anthracene-initiated Syrian golden hamsters does not lead to the formation of epithelial tumors and leaves the epidermis essentially unchanged.
However, previous histological studies by others have shown that hamster epidermis can be hyperplastically transformed by a single application of TPA but that the tissue is capable of gradually adapting to the drug after extended TPA exposure. We have investigated the response of hamster back epidermis to single and multiple treatments with increasing doses of TPA with regard to histological, proliferative, and biochemical alterations, and we show that in our animal strain the dorsal epidermis is resistant to even a single exposure to TPA, although the clearance rate of TPA is comparable to that in mouse epidermis and the metabolism of the substance is negligible.
In contrast, the epidermis could be moderately stimulated by a single application of the nonpromoting calcium ionophore A 23187 and exhibited a strong proliferate and hyperplastic response following the simultaneous exposure to the calcium ionophore and TPA. Both types of hyperproliferation did not reveal an initial depression of the proliferative activity and were accompanied by typical alterations of the keratin polypeptide pattern, which was not detectable after treatment with TPA alone.