Nadao Kinoshita

Immunohistochemical Characterization of Cellular Infiltrates in Epidermal Tumors Induced by Two-stage and Complete Chemical Carcinogenesis in Mouse Skin

We investigated the population and pattern of the infiltrated cells in both benign and malignant epidermal tumors which were induced chemically with benzo(a)pyrene (B(a)P) in murine skin. In benign papillomas, which were evolved by a two stage carcinogenesis regimen, a slight to mild inflammatory infiltration around the tumors was observed, and cells infiltrating into the tumor nests were rarely seen. In carcinomas, which were produced by a complete carcinogenesis regimen, a dense inflammatory infiltration was observed around the tumor nests. The infiltrated cells were characterized as T‐lymphocytes, macrophages, and neutrophils. Natural killer (NK) cells were found around and in the tumor nests, but their number was small. Both T‐lymphocytes and macrophages were found to invade the tumor nests in squamous cell carcinoma whose duration was more than four weeks. This experimental carcinogenesis animal model allows the detailed quantitative and functional analysis of the infiltration of immunocompetent cells into epidermal tumors.

Effects of Krestin (PSK) on Tumorigenesis Induced by Two-stage and Complete Chemical Carcinogenesis

The effects of PSK on tumorigenesis in mouse skin were investigated either when mouse skins were initiated by benzo(a)pyrene and promoted by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (Group I, two‐stage carcinogenesis) or when both initiated and promoted by benzo(a)pyrene (Group II, complete carcinogenesis). Twelve mice in each group were fed chow with or without 0.4% PSK. This concentration of PSK was determined by calculation to give mice enough PSK to exert antitumorigenic activity without cytotoxicity. By the end of the experimental periods (26 weeks), two carcinoma‐burdened mice in Group I without PSK were dead, but no carcinomas at all were identified in the mice fed with PSK, although considerable numbers of papillomas developed in both groups. In Group II, carcinomas started to evolve at the 15th week of the experiment regardless of PSK feeding. The number of carcinomas observed in the mice fed with PSK in Group II was statistically significantly lower than that in the mice fed without PSK. Histologically, mild inflammatory infiltrations were seen around the papillomas, and moderate to dense infiltrations, mainly composed of neutrophils, T lymphocytes, and macrophages, were observed in squamous cell carcinomas. There were apparently no significant differences in the number of the infiltrating cells around carcinomas in PSK (+) and PSK (−) groups in both early and fully developed lesions. However, considerable numbers of cells infiltrating into the nests were observed in the early lesions of elicited carcinomas in the mice fed with PSK, while such cells were rarely seen in carcinoma nests in the group without PSK at that stage. The multi‐stage carcinogenesis regimen which evokes both benign and malignant epidermal tumors in mouse skin should provide insights into the function of the specific infiltration of immuno‐competent cells and should also be a valid system for the quantitative and qualitative analysis of the anti‐tumor effects of immunopotentiators such as PSK.