Effects of Depot Injections of Retinyl Palmitate on 7,12-Dimethylbenz[a]anthracene-induced Preneoplastic Changes in Rat Skin2

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Abstract
The preneoplastic skin changes usually induced by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) to adult rat skin did not appear when animals were treated locally with depot im injections of high doses of retinyl palmitate (RP) prior to exposure to the carcinogen. The epidermal histology after RP-DMBA treatment was similar to that seen in areas exposed to RP alone. Keratinization was inhibited but there was no cellular atypia, evidence of cell injury, or mucous metaplasia. Other features were hyperplasia with acanthosis and thickened stratum granulosum, parakeratosis, intercellular edema, and loss of hair overlying the injection site. Ultrastructurally, the epidermal cells contained conspicuously fewer tonofibrils and increased dense chromatin, when compared to control cells. Skin changes observed following treatment of littermates with DMBA alone included the appearance of giant tumor cells, dyskeratotic cells, nuclear hyperchromatism, increased nucleocytoplasmic ratio, and pleomorphic nuclei and nucleoli. Loss of desmosomes, increased tonofibrils, and defects in the basement membrane with epithelial projections into the dermis were also seen. These preneoplastic changes did not regress when application with DMBA was discontinued after 6 weeks; exposure to the carcinogen for longer than 6 weeks resulted in an exacerbation of the abnormal state. RP had profound effects on rat epidermis that interfered with the effects of a potent skin carcinogen. The mechanisms underlying the phenomenon have not been defined. The use of depot injections of the vitamin which avoids both systemic toxicity and the local irritation seen with topical exposure could serve as a model in which the anticarcinogenesis properties of retinoids could be explored.