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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Colburn, N. H. Articles by Head, R. Search for Related Content PubMed PubMed Citation Articles by Colburn, N. H. Articles by Head, R.

Decrease of Epidermal Histidase Activity by Tumor-promoting Phorbol Esters¹

Departments of Dermatology and Biological Chemistry, The University of Michigan Medical School, Ann Arbor, Michigan 48104

² Recipient of NIH Special Research Fellowship 5 FO3-AM54259-02. To whom requests for reprints should be addressed, at Department of Enivronmental and Industrial Health, 1620 School of Public Health I, The University of Michigan, Ann Arbor. Mich. 48104.

The potent skin tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates epidermal macromolecular synthesis as well as proliferation, but little is known of specific functional aberrations produced by TPA. This report presents results of a study on the effects of TPA on epidermal histidase (L-histidine ammonia lyase), an enzyme found in normal epidermis but not in dermis or in mouse squamous cell carcinomas. Histidase activity was assayed on postmitochondrial supernatants obtained from hairless mouse epidermis after removal by keratotome. Topical TPA treatment at doses active in tumor promotion (1.7 to 17.0 nmoles/application) produced dose-dependent decreases in epidermal histidase specific activity at 19 hr posttreatment. The onset of the decrease occurred at 12 hr with recovery to control level specific activity by 5 days, showing kinetics similar to those obtained for stimulation of DNA synthesis. This decrease in histidase could not be attributed to a general inhibition of soluble protein synthesis or to the appearance of an inhibitor of histidase activity. The strong promoter TPA produced a greater histidase decrease than did the moderate promoter and mitogen 12,13-didecanoyl phorbol at equimolar dose, while phorbol, a nonpromoter and nonmitogen, produced no effects on histidase. The relationship of this histidase depression to tumor promotion and not initiation is further indicated by the finding that (a) Tween 60, a structurally unrelated tumor promoter, also produced a decrease in histidase; and (b) the tumor initiator urethan and an initiating dose of 9,10-dimethylbenz(a)anthracene showed no effects on histidase activity.

¹ Presented in part at the Annual Meeting of the American Association for Cancer Research, March 27, 1974. Supported in part by the Babcock Dermatological Endowment Fund, NIH Grant AM 15740-01, and NIH Contract NO 1 CP 33303 to J. J. Voorhees and E. A. Duell.

Received 2/10/75. Accepted 8/ 7/75.

This article has been cited by other articles:

				L. Lee and I. Weinstein Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors Science, October 20, 1978; 202(4365): 313 - 315. [Abstract] [PDF]