PMID: 109195Jul 1, 1979

Effects of structural changes on the tumor-promoting activity of phorbol myristate acetate on mouse skin

Cancer Research
B L Van DuurenI Seidman

Abstract

4a alpha-Phorbol-9,9a-didecanoate, 4a alpha-phorbol-9-myristate-9a-acetate, and phorbol-9-myristate-9a-acetate-3-aldehyde were tested for skin tumor-promoting activity by using 7,12-dimethylbenz(a)anthracene as the initiating agent. There were 30 female ICR/Ha mice/group, and tests were continued for 434 to 461 days. 4a alpha-Phorbol-9,9a-didecanoate and 4a alpha-phorbol-9-myristate-9a-acetate were devoid of tumor-promoting activity. Phorbol-9-myristate-9a-acetate-3-aldehyde resulted in 10 mice with papillomas, 2 of which also bore squamous carcinomas of the skin. The positive control group, in which phorbol myristate acetate was used as promoting agent, resulted in 30 mice bearing multiple papillomas and 15 bearing squamous carcinomas of the skin. The effects of structural and stereochemical changes on tumor-promoting activity suggest that a primary interaction of the phorbol ester series is binding at specific sites on the plasma membrane.

Related Concepts

Aldehydes
Squamous Cell Carcinoma
Decanoates
Drug Augmentation
Mouse, Inbred ICRC
Neoplasms, Experimental
Papillomatosis
Phorbols
Malignant Neoplasm of Skin
Structure-Activity Relationship

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