A large body of information on the modulation by active tumor-promoting agents of cellular immunity in vitro, and a few reports of similar activity in vivo raises the question whether immune modulation plays a role in tumorigenesis by the same agents in mouse epidermis. A major obstacle to making further conclusions regarding this question is lack of experimental findings on the immunomodulatory activity of active promoters and their inactive but inflammatory analogs following topical application protocols used in standard tumorigenesis experiments. In our preliminary experiments marked qualitative differences between promoter effects on splenic leukocytes in vitro, and following topical application in vivo, have been found. These results, therefore, stress the need for experiments using the latter protocols in assessing a role for immunomodulation in tumorigenesis or carcinogenesis. Among cell types reported responsive to promoter effects in vitro are hematopoietic stem and granulocyte/macrophage progenitor cells. Since granulocytes and macrophages are also assumed to be implicated in the inflammatory response observed with all active promoting agents, a possible interrelation between promotion, inflammation, hematopoiesis and skin immunocytology is therefore indicated for further study. A study of this kind is proposed herein and will have the following four objectives: A. Determination of the cell population responding to promoters in the spleen. B. Study of the relationship of inflammation to the spleen response. C. Determination of the role of modulation of hematopoiesis in the above. D. Analysis of immunofunctional cell populations in the skin during topical promoter application. The common approach to the three objectives is: i) The use of agents with different tumor-promoting and inflammatory activities. ii) The use of agents which modify tumor promotion and inflammation. iii) Comparison of short and prolonged exposures to agents with short-term and prolonged inflammatory activity.
