This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Argyris, T. S. Search for Related Content PubMed PubMed Citation Articles by Argyris, T. S.

Nature of the Epidermal Hyperplasia Produced by Mezerein, a Weak Tumor Promoter, in Initiated Skin of Mice¹

Department of Pathology, Upstate Medical Center, Syracuse, New York 13210

Mezerein is widely known as being a weak epidermal tumor promoter, but it is said to be a good agent for producing epidermal hyperplasia. Indeed, its ability to produce hyperplasia has been likened to that of 12-O-tetradecanoylphorbol-13-acetate (TPA), which by contrast is a powerful tumor promoter. There is not sufficient information about the nature of the epidermal hyperplasia produced by mezerein to warrant the conclusion that it produces a hyperplasia similar to that produced by TPA. We have undertaken to investigate in detail the epidermal hyperplastic growth produced by mezerein in order to help us understand why mezerein is a weak tumor promoter in mouse skin.

The application of 17 nmol of mezerein on skin initiated 7 days previously with 200 nmol of dimethylbenzanthracene results in a vigorous epidermal hyperplasia comparable to that produced by the application of 17 nmol of TPA, as judged by changes in epidermal wet weight, total protein and DNA, the number of nucleated cell layers, the number of basal and suprabasal nuclei per mm interfollicular epidermis, and the epidermal mitotic activity.

However, with multiple applications of 17 nmol of mezerein, the initial hyperplasia is followed by a decrease in mitotic activity and the appearance of an epidermal hyperplasia which is quite different from that produced by multiple applications of 17 nmol of TPA. It is characterized by a decrease in the size of the basal and suprabasal cells. Nuclei appear dense and they are oriented parallel to the basement membrane. There is little stratum granulosum so characteristic of TPA-treated epidermis. Moreover, there are areas in which the hyperplastic epidermis is covered with thick layers of parakeratotic or abnormally keratinized cells.

Thus, we suggest that one reason that mezerein is a weak promoter of epidermal tumorigenesis in the skin of mice is that, although it initially produces hyperplasia similar to that produced by TPA, later events following repeated applications are different, and the initial epidermal hyperplasia cannot be maintained.

¹ This work supported by NIH Grants AM 18219 and AG 01324.

Received 9/24/82. Accepted 1/ 6/83.