Studies on Certain Proteins in Normal and Pathological Epidermis

Abstract

THE manner by which carcinogenic agents induce neoplastic growths is unknown in spite of the large amount of work which has been carried out on the chemistry of carcinogenesis. Epidermis was chosen as the tissue of choice for the work reported here for reasons given previously (Carruthers, 1950). Various stages in the malignant process such as methylcholanthrene-induced hyperplastic epidermis, papillomas and squamous-cell carcinomas were investigated. These phases were studied because large changes were sought in the present study particularly since the various degrees of intermediate and late epidermal hyperplasia show little, if any, significant chemical alterations (Carruthers, 1950). Also the recent studies of Rudall (1952) on the structural (urea extractable) proteins of beef snout epidermis offer some background for the proposed work. The structural proteins of epidermis may play a role in the adhesiveness of squamous cells (Rudall, 1952) and alterations in such proteins may account for the invasiveness and metastasis of skin carcinomas. In addition to the urea extractable protein (Carruthers, Woernley, Baumler and Kress, 1955) Croton oil treated epidermis served as a control since a huge number of normal mice would have to be sacrificed to yield sufficient epidermis from which to extract the proteins in large enough quantities for characterization. Croton oil treated epidermis shows a relatively benign hyperplasia since numerous applications of this material are necessary to elicit a good carcinogenic response in many mice (Roe, 1956). The epidermis was removed from the dermis at 50°C. (Baumberger, Suntzeff and Cowdry, 1942). Papillomas from many mice were pooled and then stored at 0-4°in 95 per cent alcohol until the amount was ample for extraction of the various proteins. Methylcholanthrene induced squamous-cell carcinomas were pooled from some 15 to 20 mice, and a small piece from each cancer was fixed and stained for histological examination. The remainder was cleaned of necrotic and connective tissue and placed in 95 per cent alcohol. The urea extract-

Differences in the Urea-extracted Proteins of Mouse Epidermis and Squamous cell Carcinomata Determined by Fluorescence Microscopy

“…These ureaextracted proteins are extracted with 6 mol/l urea and precipitated maximally at pH (Carruthers et al, 1955(Carruthers et al, , 1957Rudall, 1.952), and are sometimes denoted as the urea-extractable 5-5 proteins; herein for simplicity they are called the urea proteins. Previous studies indicated that epidermis contained urea-extractable antigens which were absent, or present in small amounts, in carcinoma and that carcinoma contained urea-extractable antigens which were absent or present in small amounts in epidermis.…”

Differences in the Urea-Extracted or Fibrous Proteins of Mouse Epidermis at Various Stages of Malignant Transformation

“…The 1 The author acknowledges the excellent technical assistance of Mrs. A. Heining and McKenna and Miss A. Baumler. C a r r u t h e r s urea-extractable or fibrous proteins [16] were solubilized from the related epidermal tissues with 6 m urea and were then isolated by precipitation at pH 5.5 [9,10,16]; they are designated herein simply as the urea proteins. In this report further evidence is submitted on the nature of the differences in the urea proteins of epidermis at various stages of neoplastic transfor mation.…”

Stereospecificity of Esterases Hydrolyzing Oxazepam Acetate

“…Fractionation was accomplished by ~ltracentrifugation~ with a combination of previous methods (10,11) according to Scheme I. All Results are averages of thren?…”