The Histologic Study of Skin Tumors Induced by Ethyl Carbamate and Its Metabolites

Ahn, Sung Ku; Chung, Joon; Park, Yoon Kee; Park, Kwang Kyun

Abstract

BACKGROUND: Ethyl crbmate(EC) has been identified at low microgram quantities in various fermented beverages, destiled products and tobacco smoke. EC has long been known as a carcinogen. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide(VCO). VC and VCO proved to be much more carcirogenic than EC. OBJECT: The objective of this study is to compare the potency of carcinogenic ability and histologic changes in skin tumors induced by EC, VC, or VCO.
METHODS
In this exeriment, the tumor induction was performed by painting the mouse skin once a week for five weeks with EC, VC and VCO solution, and then 12-0-tetradecanoyl-phorbol-13-acetate(TP2) was treated in the same manner twice a week for 35 weeks. We biopsied the skin at B 0, 15, 25, 30 and 35 weeks and stained the specimens with hematoxylineosin.
RESULTS
The time period for the first appearance of papilloma was 6 weeks in the VC-TPA and VCO-TPA group, but, 15 weeks in the EC TPA group. The average number of papilloma showed a statistically sign.ficant difference after 15 weeks between the EC-TPA, VC-TPA and VCO-TPA group. The occurrence of keratoacanthoma and squamous cell carcinoma was 16 and 21 weeks respectively. Histologic changes, such as epidermal layers, pseudohorncysts, degree of hyperkeratosis, hypergranulosis, dysplasia and dyskeratotic cells were more prominent in the papil loma than in the non-papilloma lesion. Dermal changes disclosed similiar findings, that is, increased dermal thicknes, proliferation of vessels and hair follicles, and fibrosis of the dermis. Squamous cell carcinomis and keratoacanthomas were produced only in the VCO-TPA group.
CONCLUSION
From the above results it is concluded that VC and VCO have a more potent carcinogenic potential than EC. Various skin tumors, such as papilloma, keratoacanthoma or squamous cell carcinoma were prorduced by the above carcinogens.