Abstract

Chemically induced epiderml carcinogenesis is usually divided into two stages, the initiation and promotion. The initiation involves conversion of some epidermal cells into latent neoplastic cells and the promotion is proliferation of the transformed cells. As immunosurveillence is thought to be a host defense against tumors, Langerhans cells, being essential in initiation of local cutaneous immunologic reaction, is suggested to be important in the carcingenesis of the epidermis. This study is attempted to investigate the epidermal proliferative changes in mice induced by application of 12-0-tetradecanoy1-phorbol-13-acetate(TPA) on the skin initiated with 7, 12-dimethylbenzanthracene(DMBA) and its relationship with Langerhans cell. Ninty five male inbred BALB/c mice weighing 20~25 g were divided into five groups; the 33 week-group, the 21 week-group, the 12 week-group and the 4 week-group according to the duration of carcinogen application, and the control group. The carcingen was applied with a brush on the dorsal skin of mice after depilation. Ten days after application of 800 nmole DMBA in 0.4 cc acetone, 20 nmole TPA in 0.4 cc acetone was applied twice per week and the control group was applied with the same amount of acetone for 4 weeks. Animals were sacrificed 3 days after the last application of TPA. One hour before sacrifice, bromodeoxyuridine(BrdU) (1 mg/g) was injected via the tail artert for BrdU stain of S phase cells. A strip of dorsal skin was used for hematoxylineosin stain, immunohistochemical stain for BrdU and la antigen of Langerhans cell, and flow cytometry. The results are as follows: 1. Cellular proliferation, hyperkeratosis and dysplasia of the epidermis were increased in relation to duration of carcingen application. Papillomas were developed 12 weeks after application of the carcingen. 2. BrdU labelling and proliferative indices of the 20 weeks' application group were significantly higher than those of the 12 weeks' application group. The number of Langerhans cell was decreased markedly ater 4 week' application of the carcinogen. 3. All epiedrmal lesions including a case of squamous cell carcinoma were diploidy in flow cytometry. It is thought that disturbance of immunosurveillence, caused by depletion of Langerhans cell, may permit proliferation of epidermal cells. Although abnormal quantitative change of nuclear DNA has not occurred even when the epidermal proliferative activity and dysplastic change were increased markedly, it is thought that the occurrence of structural change of chromosome is remained to be clarified.

• Keywords: Carcinogenesis;Epidermal proliferation;Langerhans cell;Flow cytometry