Enhancement of Carcinogenesis by Prostaglandins in Male Albino Swiss Mice2

Abstract

The effects of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) on the development of skin tumors were studied in male albino Swiss mice treated with a carcinogen. The formation of squamous cell carcinoma was markedly enhanced by concomitant PGE2 and PGF2α administration to mice treated with 3-methylcholanthrene (MCA) for 2 months, whereas only epidermal hyperplasia occurred in mice treated with MCA alone for 2 months. Radioisotope studies showed an increase in incorporation of [3H]thymidine, followed by [3H]uridine, [3H]proline, and [3H]leucine in the neoplastic cells of mice treated with MCA and prostaglandin as compared to the incorporation seen in mice treated with MCA alone, prostaglandin alone, or in control mice. Light and electron microscopic autoradiography revealed a significant increase in labeled cells and grain distribution of [3H]thymidine over nuclei, [3H]uridine over nucleoli, and [3H]leucine over the cytoplasm of neoplastic cells compared to the increase in distribution observed in hyperplastic or control epidermal cells. Electron microscopy showed the predominance of neoplastic squamous cells with large nuclei, an increased nuclearcytoplasmic ratio, dark and light cells with distinct ultrastructural features, increased polysome and dense granule populations, altered mitochondria, and discontinuities of the basement membrane in mice treated with MCA and PGF2α or MCA and PGE2. Hyperplastic and dysplastic cellular changes only appeared in the epidermis of MCA-treated mice. A moderate increase in polysomes, tonofilaments, and enlarged nuclei and intercellular spaces occurred in prostaglandin-treated mice. These findings demonstrate that prostaglandins are important as cocarcinogens for cutaneous carcinogenesis.