Mechanism of Experimental Tumorigenesis. II. Effect of Mole Ratio Distribution of Span 60 and Span 20 Derivatives on Hyperplasia in Mouse Epidermis23

Abstract

The evolution, general development, persistence, and nature of the hyperplastic response in the interfollicular epidermis of the back of white male mice of the tumor-resistant strain used in this laboratory was followed for 30 days. Ethylene oxide (EO) derivatives of technical Span 60 (sorbitan monostearate) and Span 20 (sorbitan monolaurate) were deliberately selected, which contained 5, 10, 15, 20, 30, 40, 60, and 100 EO units. The skin was painted 6 times a week with approximately 0.18 m aqueous solutions and dispersions of the compounds. Except for compounds containing, on the average, 5 and 100 EO units, which were biologically somewhat weaker, all Span 60 EO derivatives produced a high degree of regular and persisting epidermal hyperplasia. The hyperplasia developed on the 2d day and was a direct result of an intense cellular proliferation—the percentage of mitoses increased 5- to 15-fold. The character of this hyperplastic state differed completely from that produced by a similar continued local carcinogen treatment. Accordingly the hyperplasia-causing capacity of an EO derivative of Span 60, which contains, on the average, 20 EO units, i.e., a product of Tween 60 character, is due to the compound itself. None of the EO derivatives of Span 20 caused either a high degree of or a persisting hyperplasia. Merely the addition of EO chains to Spans, in general, was not responsible for the effect, because the original Span type itself was decisive. This fact supports the significance of the physicochemical nature of the fatty acid ester-type, hyperplasia-causing agent.